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TANAKA Hirokazu

    Kindai University Hospital　Clinical Professor
Last Updated :2024/04/25

Researcher Information

URL

J-Global ID

Research Interests

  • 造血   活性酸素種   造血器腫瘍   NF-κB   アポトーシス   細胞周期   造血幹細胞   鉄過剰   ストローマ細胞   鉄・硫黄クラスター   白血病幹細胞   分化   P38MAPK   アナモルシン   ES細胞   白血病   白血病原因遺伝子   

Research Areas

  • Life sciences / Hematology and oncology

Academic & Professional Experience

  • 2023/04 - Today  Kindai UniversityFaculty of Medicine Department of Medicine教授

Education

  • 1997/04 - 2001/03  大阪大学大学院  医学系研究科
  • 1989/04 - 1995/03  Hamamatsu University School of Medicine

Association Memberships

  • American Society of Hematology   THE JAPAN SOCIETY OF TRANSFUSION MEDICINE AND CELL THERAPY   THE JAPAN SOCIETY FOR TRANSPLANTATION   THE JAPANESE SOCIETY OF HEMATOLOGY   THE JAPANESE SOCIETY OF INTERNAL MEDICINE   

Published Papers

  • Yuji Shimura; Hirohiko Shibayama; Aya Nakaya; Ryosuke Yamamura; Kazunori Imada; Hitomi Kaneko; Hitoshi Hanamoto; Shin-Ichi Fuchida; Hirokazu Tanaka; Satoru Kosugi; Miki Kiyota; Toshimitsu Matsui; Junya Kanda; Masato Iida; Mitsuhiro Matsuda; Nobuhiko Uoshima; Masaru Shibano; Takahiro Karasuno; Tsuneyoshi Hamada; Kensuke Ohta; Tomoki Ito; Hideo Yagi; Satoshi Yoshihara; Chihiro Shimazaki; Shosaku Nomura; Masayuki Hino; Akifumi Takaori-Kondo; Itaru Matsumura; Yuzuru Kanakura; Junya Kuroda
    International journal of hematology 2023/09 
    To investigate the real-world clinical outcomes and management of novel drug-containing therapies for newly diagnosed multiple myeloma (MM) patients, we retrospectively analyzed data on the first-line treatment for newly diagnosed transplant-ineligible MM patients from Kansai Myeloma Forum, a registry network in Japan. A total of 598 patients treated with novel drugs between March 2007 and February 2018 were analyzed. Regimens used were VD (n = 305), Rd (n = 103), VMP (n = 97), VCD (n = 71), and VRd (n = 22). Younger patients tended to receive VRd or VCD, whereas the regimen with the highest median patient age was Rd. More than three-quarters of patients in the Rd group received a reduced dose of lenalidomide. The Rd and VRd groups had a relatively high incidence of infection and skin complications, and the VMP group had the highest incidence of peripheral neuropathy. Overall response rate did not differ significantly between regimens. Multivariate analysis in all patients revealed several poor prognostic factors, such as poor performance status. Novel drug-containing regimens for newly diagnosed MM showed a durable response with manageable AEs in the real-world setting.
  • Takahiro Haeno; Shinya Rai; Yoshiaki Miyake; Maiko Inoue; Ko Fujimoto; Aki Fujii; Yoshio Iwata; Shuji Minamoto; Takahide Taniguchi; Hiroaki Kakutani; Hiroaki Inoue; Takahiro Kumode; Kentaro Serizawa; Yasuhiro Taniguchi; Chikara Hirase; Yasuyoshi Morita; Hirokazu Tanaka; Yoichi Tatsumi; Takashi Ashida; Itaru Matsumura
    Journal of clinical and experimental hematopathology : JCEH 63 (2) 99 - 107 2023/06 
    We retrospectively evaluated long-term outcomes of high dose chemotherapy followed by autologous stem cell transplant (HDC/ASCT) in patients with diffuse large B-cell lymphoma (DLBCL). Between 2004 and 2020, 46 DLBCL patients received HDC/ASCT in our institution, including 12 patients (26.1%), who received as an upfront setting (UFS). At a median follow-up time of 69 months (range, 2-169 months), the 5-year progression-free survival (PFS) rates were 82.5% (95%CI, 46.1-95.3%) in the UFS, and 57.8% (95%CI, 38.1-73.2%) in the relapsed or refractory (R/R) patients (n=34), respectively. The 5-year PFS rates were 62.3% (95%CI, 34.0-81.3%) in primary resistant (n=13) or early relapsing (within 1 year from the initial diagnosis) patients (n=4), and 53.3% (95%CI, 25.9-74.6%) in those relapsing >1 year after the initial diagnosis (n=17), with no statistically significant difference (p=0.498). In R/R patients, multivariate analysis showed that the remission status before HDC/ASCT was an independent poor prognostic factor for progression-free survival (hazard ratio [HR], 17.0; 95%CI, 3.35-86.6; p=0.000630) and high-risk category in the international prognostic index for OS (HR, 9.39; 95%CI, 1.71-51.6; p=0.0100). The incidence of non-relapse mortality by 5 years, and 10 years were 12.2%, and 15.2%, respectively. Eleven patients (23.9%) developed second malignancies, which was the most frequent late complication after HDC/ASCT, with 5-year, and 10-year cumulative incidence of 16.9%, 22.5%, respectively. In conclusion, HDC/ASCT is effective for chemo-sensitive R/R DLBCL regardless of the timing and lines of therapy. However, careful observation is required, considering the long-term complications such as secondary malignancies.
  • 田中 宏和; 芹澤 憲太郎; 松村 到
    日本臨床 (株)日本臨床社 81 (6) 806 - 812 0047-1852 2023/06
  • Yutaka Shimazu; Junya Kanda; Satoru Kosugi; Tomoki Ito; Hitomi Kaneko; Kazunori Imada; Yuji Shimura; Shin-Ichi Fuchida; Kentaro Fukushima; Hirokazu Tanaka; Satoshi Yoshihara; Kensuke Ohta; Nobuhiko Uoshima; Hideo Yagi; Hirohiko Shibayama; Ryosuke Yamamura; Yasuhiro Tanaka; Hitoji Uchiyama; Yoshiyuki Onda; Yoko Adachi; Hitoshi Hanamoto; Ryoichi Takahashi; Mitsuhiro Matsuda; Takashi Miyoshi; Teruhito Takakuwa; Masayuki Hino; Naoki Hosen; Shosaku Nomura; Chihiro Shimazaki; Itaru Matsumura; Akifumi Takaori-Kondo; Junya Kuroda
    Scientific reports 13 (1) 5159 - 5159 2023/03 
    Novel therapeutic drugs have dramatically improved the overall survival of patients with multiple myeloma. We sought to identify the characteristics of patients likely to exhibit a durable response to one such drug, elotuzumab, by analyzing a real-world database in Japan. We analyzed 179 patients who underwent 201 elotuzumab treatments. The median time to next treatment (TTNT) with the 95% confidence interval was 6.29 months (5.18-9.20) in this cohort. Univariate analysis showed that patients with any of the following had longer TTNT: no high risk cytogenic abnormalities, more white blood cells, more lymphocytes, non-deviated κ/λ ratio, lower β2 microglobulin levels (B2MG), fewer prior drug regimens, no prior daratumumab use and better response after elotuzumab treatment. A multivariate analysis showed that TTNT was longer in patients with more lymphocytes (≥ 1400/μL), non-deviated κ/λ ratio (0.1-10), lower B2MG (< 5.5 mg/L) and no prior daratumumab use. We proposed a simple scoring system to predict the durability of the elotuzumab treatment effect by classifying the patients into three categories based on their lymphocyte counts (0 points for ≥ 1400/μL and 1 point for < 1400/μL) and κ/λ ratio (0 points for 0.1-10 and 1 point for < 0.1 or ≥ 10) or B2MG (0 points for < 5.5 mg/L and 1 point for ≥ 5.5 mg/L). The patients with a score of 0 showed significantly longer TTNT (p < 0.001) and better survival (p < 0.001) compared to those with a score of 1 or 2. Prospective cohort studies of elotuzumab treatment may be needed to validate the usefulness of our new scoring system.
  • 田中 宏和; 芹澤 憲太郎; 松村 到
    血液内科 (有)科学評論社 86 (2) 266 - 271 2185-582X 2023/02
  • Ryosuke Fujiwara; Yasuhiro Taniguchi; Shinya Rai; Yoshio Iwata; Aki Fujii; Ko Fujimoto; Takahiro Kumode; Kentaro Serizawa; Yasuyoshi Morita; J Luis Espinoza; Hirokazu Tanaka; Hitoshi Hanamoto; Itaru Matsumura
    Biochemical and biophysical research communications 626 156 - 166 2022/08 
    We previously reported that the antipsychotic drug chlorpromazine (CPZ), which inhibits the formation of clathrin-coated vesicles (CCVs) essential for endocytosis and intracellular transport of receptor tyrosine kinase (RTK), inhibits the growth/survival of acute myeloid leukemia cells with mutated RTK (KIT D816V or FLT3-ITD) by perturbing the intracellular localization of these molecules. Here, we examined whether these findings are applicable to epidermal growth factor receptor (EGFR). CPZ dose-dependently inhibited the growth/survival of the non-small cell lung cancer (NSCLC) cell line, PC9 harboring an EGFR-activating (EGFR exon 19 deletion). In addition, CPZ not only suppressed the growth/survival of gefitinib (GEF)-resistant PC9ZD cells harboring T790 M, but also restored their sensitivities to GEF. Furthermore, CPZ overcame GEF resistance caused by Met amplification in HCC827GR cells. As for the mechanism of CPZ-induced growth suppression, we found that although CPZ hardly influenced the phosphorylation of EGFR, it effectively reduced the phosphorylation of ERK and AKT. When utilized in combination with trametinib (a MEK inhibitor), dabrafenib (an RAF inhibitor), and everolimus (an mTOR inhibitor), CPZ suppressed the growth of PC9ZD cells cooperatively with everolimus but not with trametinib or dabrafenib. Immunofluorescent staining revealed that EGFR shows a perinuclear pattern and was intensely colocalized with the late endosome marker, Rab11. However, after CPZ treatment, EGFR was unevenly distributed in the cells, and colocalization with the early endosome marker Rab5 and EEA1 became more apparent, indicating that CPZ disrupted the intracellular transport of EGFR. These results suggest that CPZ has therapeutic potential for NSCLC with mutated EGFR by a novel mechanism different from conventional TKIs alone or in combination with other agents.
  • Takahide Taniguchi; Shoko Nakayama; Hirokazu Tanaka; Shinya Rai; Chikara Hirase; Yasuyoshi Morita; Yoichi Tatsumi; Takashi Ashida; Mitsuhiro Matsuda; Shigeo Hashimoto; Itaru Matsumura
    British journal of haematology 198 (2) 360 - 372 2022/04 
    We previously reported that a novel haemoglobin-platelet index (HPI) based on anaemia and thrombocytopenia was useful to predict the prognosis of patients with diffuse large B-cell lymphoma not otherwise specified (DLBCL NOS). Here, we analyse the utility of HPI in a new validation cohort with DLBCL NOS (n  = 94). As a result, we confirm that HPI was effective for differentiating progression-free survival (PFS) and overall survival in this validation cohort. So, we further compare the utility of HPI with previously reported prognostic markers such as the National Comprehensive Center Network-International Prognostic Index (NCCN-IPI), Glasgow prognostic score (GPS), and platelet-albumin (PA) score, using a larger number of 160 patients consisting of the derivation cohort (n  = 66) and a validation cohort (n  = 94). As a result, the patients with a higher HPI score had significantly worse outcomes, and HPI predicted the prognosis of DLBCL NOS independently of NCCN-IPI. HPI was more sensitive than GPS and almost the same as PA score in predicting PFS. Moreover, the patients whose lymphoma cells were positive for interleukin-6 (IL-6) (75/111 cases) judged by immunohistochemical staining had significantly lower haemoglobin levels and platelet counts than IL-6-negative cases (36/111 cases), suggesting the involvement of IL-6 produced by lymphoma cells in anaemia and thrombocytopenia in DLBCL NOS patients.
  • Takahiro Kumode; Hirokazu Tanaka; Jorge Luis Esipinoza; Shinya Rai; Yasuhiro Taniguchi; Ryosuke Fujiwara; Keigo Sano; Kentaro Serizawa; Yoshio Iwata; Yasuyoshi Morita; Itaru Matsumura
    International journal of hematology 115 (3) 310 - 321 2022/03 
    C-type lectin-like receptor 2 (CLEC-2) expressed on megakaryocytes plays important roles in megakaryopoiesis. We found that CLEC-2 was expressed in about 20% of phenotypical long-term hematopoietic stem cells (LT-HSCs), which expressed lower levels of HSC-specific genes and produced larger amounts of megakaryocyte-related molecules than CLEC-2low LT-HSCs. Although CLEC-2high LT-HSCs had immature clonogenic activity, cultured CLEC-2high LT-HSCs preferentially differentiated into megakaryocytes. CLEC-2high HSCs yielded 6.8 times more megakaryocyte progenitors (MkPs) and 6.0 times more platelets 2 weeks and 1 week after transplantation compared with CLEC-2low LT-HSCs. However, platelet yield from CLEC-2high HSCs gradually declined with the loss of MkPs, while CLEC-2low HSCs self-renewed long-term, indicating that CLEC-2high LT-HSCs mainly contribute to early megakaryopoiesis. Treatment with pI:C and LPS increased the proportion of CLEC-2high LT-HSCs within LT-HSCs. Almost all CLEC-2low LT-HSCs were in the G0 phase and barely responded to pI:C. In contrast, 54% of CLEC-2high LT-HSCs were in G0, and pI:C treatment obliged CLEC-2high LT-HSCs to enter the cell cycle and differentiate into megakaryocytes, indicating that CLEC-2high LT-HSCs are primed for cell cycle entry and rapidly yield platelets in response to inflammatory stress. In conclusion, CLEC-2high LT-HSCs appear to act as a reserve for emergent platelet production under stress conditions.
  • Kentaro Serizawa; Hirokazu Tanaka; Takeshi Ueda; Ayano Fukui; Hiroaki Kakutani; Takahide Taniguchi; Hiroaki Inoue; Takahiro Kumode; Yasuhiro Taniguchi; Shinya Rai; Chikara Hirase; Yasuyoshi Morita; J. Luis Espinoza; Yoichi Tatsumi; Takashi Ashida; Itaru Matsumura
    International Journal of Hematology Springer Science and Business Media LLC 115 (3) 336 - 349 0925-5710 2022/03
  • Shinya Rai; Hiroaki Inoue; Kazuko Sakai; Hitoshi Hanamoto; Mitsuhiro Matsuda; Yasuhiro Maeda; Takahiro Haeno; Yosaku Watatani; Takahiro Kumode; Kentaro Serizawa; Yasuhiro Taniguchi; Chikara Hirase; J Luis Espinoza; Yasuyoshi Morita; Hirokazu Tanaka; Takashi Ashida; Yoichi Tatsumi; Kazuto Nishio; Itaru Matsumura
    Cancer science 113 (2) 660 - 673 2022/02 
    We previously examined the utility of rituximab-bendamustine (RB) in patients with follicular lymphoma (FL) exhibiting less than optimal responses to 2 cycles of the R-CHOP chemotherapy regimen. The aim of this study was to identify molecular biomarkers that can predict prognosis in RB-treated patients in the context of the prospective cohort. We first analyzed the mutational status of 410 genes in diagnostic tumor specimens by target capture and Sanger sequencing. CREBBP, KMT2D, MEF2B, BCL2, EZH2, and CARD11 were recurrently mutated as reported before, however none was predictive for progression-free survival (PFS) in the RB-treated patients (n = 34). A gene expression analysis by nCounter including 800 genes associated with carcinogenesis and/or the immune response showed that expression levels of CD8+ T-cell markers and half of the genes regulating Th1 and Th2 responses were significantly lower in progression of disease within the 24-mo (POD24) group (n = 8) than in the no POD24 group (n = 31). Collectively, we selected 10 genes (TBX21, CXCR3, CCR4, CD8A, CD8B, GZMM, FLT3LG, CD3E, EOMES, GZMK), and generated an immune infiltration score (IIS) for predicting PFS using principal component analysis, which dichotomized the RB-treated patients into immune IIShigh (n = 19) and IISlow (n = 20) groups. The 3-y PFS rate was significantly lower in the IISlow group than in the IIShigh group (50.0% [95% CI: 27.1-69.2%] vs. 84.2% [95% CI: 58.7-94.6%], P = .0237). Furthermore, the IIS was correlates with absolute lymphocyte counts at diagnosis (r = 0.460, P = .00355). These results suggest that the T-cell-associated immune markers could be useful to predict prognosis in RB-treated FL patients. (UMIN:000 013 795, jRCT:051 180 181).
  • Yutaka Shimazu; Junya Kanda; Hitomi Kaneko; Kazunori Imada; Ryosuke Yamamura; Satoru Kosugi; Yuji Shimura; Tomoki Ito; Shin-Ichi Fuchida; Hitoji Uchiyama; Kentaro Fukushima; Satoshi Yoshihara; Hitoshi Hanamoto; Hirokazu Tanaka; Nobuhiko Uoshima; Kensuke Ohta; Hideo Yagi; Hirohiko Shibayama; Yoshiyuki Onda; Yasuhiro Tanaka; Yoko Adachi; Mitsuhiro Matsuda; Masato Iida; Takashi Miyoshi; Toshimitsu Matsui; Ryoichi Takahashi; Teruhito Takakuwa; Masayuki Hino; Naoki Hosen; Shosaku Nomura; Chihiro Shimazaki; Itaru Matsumura; Akifumi Takaori-Kondo; Junya Kuroda
    Therapeutic advances in hematology 13 20406207221142487 - 20406207221142487 2022 
    BACKGROUND: Daratumumab is one of the most widely used treatments for relapsed/refractory multiple myeloma (MM) patients. However, not all patients achieve a lasting therapeutic response with daratumumab. OBJECTIVES: We hypothesized that a durable response to daratumumab could be predicted by the balance between the MM tumor burden and host immune status. DESIGN: We conducted a retrospective study using the real-world data in the Kansai Myeloma Forum (KMF) database. METHODS: We retrospectively analyzed 324 relapsed/refractory MM patients who were treated with daratumumab in the KMF database. RESULTS: In this study, 196 patients were treated with daratumumab, lenalidomide, and dexamethasone (DLd) regimen and 128 patients were treated with daratumumab, bortezomib, and dexamethasone (DBd) regimen. The median age at treatment, number of prior treatment regimens and time-to-next-treatment (TTNT) were 68, 4 and 8.02 months, respectively. A multivariate analysis showed that the TTNT under the DLd regimen was longer with either higher monocyte counts (analysis 1), higher white blood cell (WBC) counts (analysis 2), lower β2 microglobulin (B2MG < 5.5 mg/L) or fewer prior regimens (<4). No parameters were correlated with TTNT under the DBd regimen. CONCLUSION: We propose a simple scoring model to predict a durable effect of the DLd regimen by classifying patients into three categories based on either monocyte counts (0 points for ⩾200/μl; 1 point for <200/μl) or WBC counts (0 points for ⩾3500/μl; 1 point for <3500/μl) plus B2MG (0 points for <5.5 mg/L; 1 point for ⩾5.5 mg/L). Patients with a score of 0 showed significantly longer TTNT and significantly better survival compared to those with a score of 1 or 2 (both p < 0.001). To confirm this concept, our results will need to be validated in other cohorts.
  • Yoshiyuki Onda; Junya Kanda; Hitomi Kaneko; Yuji Shimura; Shin-Ichi Fuchida; Aya Nakaya; Tomoki Itou; Ryosuke Yamamura; Hirokazu Tanaka; Hirohiko Shibayama; Yutaka Shimazu; Hitoji Uchiyama; Satoshi Yoshihara; Yoko Adachi; Mitsuhiro Matsuda; Hitoshi Hanamoto; Nobuhiko Uoshima; Satoru Kosugi; Kensuke Ohta; Hideo Yagi; Yuzuru Kanakura; Itaru Matsumura; Masayuki Hino; Shosaku Nomura; Chihiro Shimazaki; Akifumi Takaori-Kondo; Junya Kuroda
    Therapeutic advances in hematology 13 20406207221104584 - 20406207221104584 2022 
    Background: Little is known about the real-world survival benefits and safety profiles of carfilzomib-lenalidomide-dexamethasone (KRd) and carfilzomib-dexamethasone (Kd). Methods: We performed a retrospective analysis to evaluate their efficacy and safety in 157 patients registered in the Kansai Myeloma Forum database. Results: A total of 107 patients received KRd. Before KRd, 99% of patients had received bortezomib (54% were refractory disease), and 82% had received lenalidomide (57% were refractory disease). The overall response rate (ORR) was 68.2%. The median progression-free survival (PFS) and overall survival (OS) were 8.8 and 29.3 months, respectively. Multivariate analysis showed that reduction of the carfilzomib dose and non-IgG M protein were significantly associated with lower PFS and reduction of the carfilzomib dose and refractoriness to prior bortezomib-based regimens were significantly associated with lower OS. A total of 50 patients received Kd. Before Kd, 96% of patients had received bortezomib (54% were refractory disease). The ORR was 62.0%. The median PFS and OS were 7.1 and 20.9 months, respectively. Based on the multivariate analysis, reduction of the carfilzomib dose and International Staging System Stage III (ISS III) were significantly associated with lower PFS. Grade III or higher adverse events were observed in 48% of KRd cases and 54% of Kd cases. Cardiovascular events, cytopenia, and infections were frequent, and 4 KRd patients died due to heart failure, arrhythmia, cerebral hemorrhage, and pneumonia. Conclusion: Our analysis showed that an adequate dose of carfilzomib is important for achieving the best survival benefits in a real-world setting. Adverse effects after KRd and Kd therapy should also be considered.
  • Aya Nakaya; Hirohiko Shibayama; Eiji Nakatani; Yuji Shimura; Satoru Kosugi; Hirokazu Tanaka; Shin-Ichi Fuchida; Junya K; a; Nobuhiko Uoshima; Hitomi Kaneko; Kazunori Imada; Kensuke Ohta; Tomoki Ito; Hideo Yagi; Satoshi Yoshihara; Masayuki Hino; Chihiro Shimazaki; Akifumi Takaori-Kondo; Junya Kuroda; Itaru Matsumura; Yuzuru Kanakura; Shosaku Nomura
    eJHaem Wiley 2 (4) 765 - 773 2688-6146 2021/11 [Refereed]
     
    A total of 129 symptomatic patients with multiple myeloma (MM) who underwent high-dose chemotherapy with autologous stem cell transplantation (HDT/ASCT) were analyzed. The 4-year overall survival (OS) of patients with maintenance (n = 82) was 80%, whereas that of patients without maintenance (n = 47) was 72% (p = 0.426). The 4-year progression-free survival (PFS) of patients with maintenance was 38%, whereas that of patients without maintenance was 27% (p = 0.088). Multivariate analysis revealed that an International Staging System score ≥2 was associated with worse PFS (hazard ratio 1.62, p = 0.043). Among the 129 patients, two were excluded owing to early relapse, 50 patients achieved complete response (CR), and 77 patients failed to achieve CR. Patients who achieved CR showed better 4-year PFS than those who failed to achieve CR (41% vs. 30%, p = 0.027); however, 4-year OS was not different (76% vs. 82%, p = 0.971). In patients who achieved CR, 4-year OS with/without maintenance was 74%/81% (p = 0.357), 4-year PFS with/without maintenance was 42%/40% (p = 0.954). In patients who failed to achieve CR, the 4-year OS with/without maintenance was 97%/91% (p = 0.107), and 4-year PFS with/without maintenance was 36%/16% (p < 0.001). In patients who failed to achieve CR, maintenance significantly improved the PFS. Maintenance after HDT/ASCT can prolong PFS in patients who fail to achieve CR in real-world settings.
  • Very elderly patients with myeloma: a multicenter retrospective analysis from Kansai Myeloma Forum(和訳中)
    岡山 裕介; 高桑 輝人; 志村 勇司; 金子 仁臣; 今田 和典; 小杉 智; 伊藤 量基; 淵田 真一; 田中 宏和; 魚嶋 伸彦; 吉原 哲; 諫田 淳也; 柴山 浩彦; 福島 健太郎; 太田 健介; 八木 秀男; 野村 昌作; 島崎 千尋; 松村 到; 高折 晃史; 保仙 直毅; 日野 雅之; 黒田 純也
    日本血液学会学術集会 (一社)日本血液学会 83回 OS1 - 1 2021/09
  • Novel web application predicting patient-specific prognosis in MM from KMF using machine learning(和訳中)
    高桑 輝人; 岡村 浩史; 島津 裕; 金子 仁臣; 今田 和典; 伊藤 量基; 山村 亮介; 太田 健介; 小杉 智; 田中 宏和; 淵田 真一; 志村 勇司; 諫田 淳也; 魚嶋 伸彦; 柴山 浩彦; 吉原 哲; 八木 秀男; 日野 雅之; 金倉 譲; 黒田 純也; 高折 晃史; 島崎 千尋; 松村 到; 野村 昌作
    日本血液学会学術集会 (一社)日本血液学会 83回 OS1 - 2 2021/09
  • Efficacy of elotuzumab plus lenalidomide and dexamethasone for MM: A retrospective analysis from KMF(和訳中)
    淵田 真一; 伊藤 量基; 小杉 智; 太田 健介; 内山 人二; 島津 裕; 恩田 佳幸; 金子 仁臣; 足立 陽子; 高桑 輝人; 諫田 淳也; 魚嶋 伸彦; 柴山 浩彦; 福島 健太郎; 田中 宏和; 志村 勇司; 今田 和典; 八木 秀男; 吉原 哲; 日野 雅之; 保仙 直毅; 高折 晃史; 松村 到; 野村 昌作; 島崎 千尋; 黒田 純也
    日本血液学会学術集会 (一社)日本血液学会 83回 OS1 - 4 2021/09
  • Teruhito Takakuwa; Kensuke Ohta; Eiji Nakatani; Tomoki Ito; Hitomi Kaneko; Shin-Ichi Fuchida; Yuji Shimura; Hideo Yagi; Hirohiko Shibayama; Junya Kanda; Hitoji Uchiyama; Satoru Kosugi; Hirokazu Tanaka; Eri Kawata; Nobuhiko Uoshima; Jun Ishikawa; Masaru Shibano; Takahiro Karasuno; Maki Shindo; Yoshifumi Shimizu; Kazunori Imada; Yuzuru Kanakura; Junya Kuroda; Masayuki Hino; Shosaku Nomura; Akifumi Takaori-Kondo; Chihiro Shimazaki; Itaru Matsumura
    Hematological oncology 39 (3) 349 - 357 2021/08 
    The plateau phase emerging during the treatment of multiple myeloma (MM) is known to last steadily for a certain period, even without treatment. Therefore, the treatment started at plateau phase is expected to be associated with a better outcome. In this study, this hypothesis was evaluated retrospectively for previously treated MM patients in Kansai Myeloma Forum database who received lenalidomide (LEN) with or without dexamethasone for the first time. Disease stability index (DSI) was defined as (maximum - minimum values of M protein during the 90 days before the start of LEN) divided by M-protein values at the start of LEN. The patients were classified into three groups: stable (S), DSI ≤ 0.25; increasing (I), DSI > 0.25 with increasing M protein; decreasing (D), DSI > 0.25 with decreasing M protein. In univariate analysis of 352 patients, DSI group "I", non-IgG type, serum albumin<3.5 g/dL, and age≥70 were statistically significant prognostic factors for both progression-free survival and overall survival. In multivariate analysis, the former 3 risk factors were statistically significant for poor overall survival. Thus, DSI is an independent prognostic factor for the treatment with LEN for previously treated MM.
  • Shinya Rai; Hiroaki Inoue; Hitoshi Hanamoto; Mitsuhiro Matsuda; Yasuhiro Maeda; Yusuke Wada; Takahiro Haeno; Yosaku Watatani; Takahiro Kumode; Chikara Hirase; J Luis Espinoza; Yasuyoshi Morita; Hirokazu Tanaka; Yoichi Tatsumi; Itaru Matsumura
    International journal of hematology 114 (2) 205 - 216 2021/08 
    The aim of this trial is to evaluate the utility of rituximab-bendamustine (R-B) for untreated advanced follicular lymphoma (FL) showing non-optimal response (nOR) to R-CHOP, and to identify clinical prognostic factors for FL patients receiving R-B. Patients who failed to achieve complete response/complete response unconfirmed (CR/CRu) [nOR-group] after 2 cycles of R-CHOP subsequently received 6 cycles of R-B. The primary endpoint was the 3-year progression-free survival (PFS) rate. Secondary endpoints included determination of prognostic factors. Fifty-six patients initially received R-CHOP, 43/56 patients (76.8%) were judged as nOR, and 33/43 patients (76.7%) completed 6 cycles of R-B. At a median follow-up of 50.6 months in the nOR-group, the 3-year PFS rate was 69.0%, and the 3-year overall survival (OS) rate was 92.7%. The most common toxicities associated with R-B were grade 3-4 lymphopenia (93.0%) and neutropenia (74.4%), both of which were manageable. A multivariate analysis including dose intensity, serum soluble interleukin-2 receptor, and FL international prognostic index-2 revealed low absolute lymphocyte count (<  869/μL) at diagnosis was an independent poor prognostic factor for both PFS and OS in the R-B-treated nOR-group. This result was further confirmed in validation cohorts including R-B-treated de novo (n = 40) and relapsed (n = 49) FL patients.
  • Teruhito Takakuwa; Ryosuke Yamamura; Kensuke Ohta; Hitomi Kaneko; Kazunori Imada; Aya Nakaya; Shin-Ichi Fuchida; Hirohiko Shibayama; Mitsuhiro Matsuda; Yutaka Shimazu; Yoko Adachi; Satoru Kosugi; Hitoji Uchiyama; Hirokazu Tanaka; Hitoshi Hanamoto; Yuji Shimura; Junya Kanda; Yoshiyuki Onda; Nobuhiko Uoshima; Hideo Yagi; Satoshi Yoshihara; Masayuki Hino; Chihiro Shimazaki; Akifumi Takaori-Kondo; Junya Kuroda; Itaru Matsumura; Yuzuru Kanakura; Shosaku Nomura
    European journal of haematology 106 (4) 555 - 562 2021/04 
    OBJECTIVES: This study aimed to investigate real-world data of ixazomib plus lenalidomide and dexamethasone (IRd) therapy for patients with relapsed and refractory multiple myeloma (RRMM). METHODS: We retrospectively analyzed 122 patients treated with IRd at 16 centers from May 2017 to January 2019 by using the Kansai Myeloma Forum database. RESULT: At the start of IRd, the median age was 72 years, 66.7% of patients had IgG type, and the median number of prior therapies was 4, comprising bortezomib (85.4%) and lenalidomide (89.3%)-based regimens. Disease progression and adverse events accounted for treatment discontinuation in 46 and 32 patients, respectively. The median overall survival (OS) was not reached, and the median progression-free survival (PFS) was 11.9 months. Sensitivity to bortezomib did not affect the PFS, whereas lenalidomide-refractory patients had significantly lower PFS than lenalidomide-sensitive patients, who were comparable to TOURMALINE-MM1 study. The patients with IgG type had significantly better PFS and OS than those with non-IgG type. CONCLUSION: This study presents the largest real-world data of patients treated with IRd in Asia. However, in real clinical practice, the patient background is different from the TOURMALINE-MM1 study, and IRd showed poor efficacy, especially in the non-IgG type and lenalidomide-refractory patients with RRMM.
  • CMML様の病型移行を来したMDSに対してアザシチジンが有効であった1例
    角谷 宏明; 口分田 貴裕; 源 周治; 頼 晋也; 森田 泰慶; 田中 宏和; 芦田 隆司; 松村 到
    臨床血液 (一社)日本血液学会-東京事務局 62 (3) 205 - 205 0485-1439 2021/03
  • Shinya Rai; Hirokazu Tanaka; J Luis Espinoza; Takahiro Kumode; Itaru Matsumura
    Leukemia research reports 15 100256 - 100256 2021 
    Acute myeloid leukemia (AML) is a heterogeneous disease often associated with poor prognosis. We previously showed that the localization of KIT-D816V at endolysosomes is critical to activate aberrant Akt signaling and Chlorpromazine (CPZ) perturbs the intracellular localization, leading to cell death in AML cells with KIT-D816V. We report that daily administration of CPZ, prescribed for controlling anxiety disorder in patient with AML harboring KIT-D816V, led to a dramatic reduction in AML cells. In vitro and in vivo experiments showed that CPZ inhibited the growth and survival of the patient-derived AML cells, implying potent efficacy of CPZ in AML with KIT-D816V.
  • Shinya Rai; Hirokazu Tanaka; Mai Suzuki; J. Luis Espinoza; Takahiro Kumode; Akira Tanimura; Takafumi Yokota; Kenji Oritani; Toshio Watanabe; Yuzuru Kanakura; Itaru Matsumura
    Nature Communications 11 (1) 4147 - 4147 2020/12 [Refereed]
     
    © 2020, The Author(s). Mutated receptor tyrosine kinases (MT-RTKs) such as internal tandem duplication of FMS-like tyrosine kinase 3 (FLT3 ITD) and a point mutation KIT D816V are driver mutations for acute myeloid leukemia (AML). Clathrin assembly lymphoid myeloid leukemia protein (CALM) regulates intracellular transport of RTKs, however, the precise role for MT-RTKs remains elusive. We here show that CALM knock down leads to severely impaired FLT3 ITD- or KIT D814V-dependent cell growth compared to marginal influence on wild-type FLT3- or KIT-mediated cell growth. An antipsychotic drug chlorpromazine (CPZ) suppresses the growth of primary AML samples, and human CD34+CD38- AML cells including AML initiating cells with MT-RTKs in vitro and in vivo. Mechanistically, CPZ reduces CALM protein at post transcriptional level and perturbs the intracellular localization of MT-RTKs, thereby blocking their signaling. Our study presents a therapeutic strategy for AML with MT-RTKs by altering the intracellular localization of MT-RTKs using CPZ.
  • Aya Nakaya; Takae Kohara; Hirohiko Shibayama; Yoshiyuki Onda; Junya Kanda; Hitomi Kaneko; Kazunori Imada; Toru Kida; Satoru Kosugi; Jun Ishikawa; Ryosuke Yamamura; Yutaka Shimazu; Hirokazu Tanaka; Shin-Ichi Fuchida; Yuji Shimura; Miki Kiyota; Katsuya Wada; Tomoki Ito; Nobuhiko Uoshima; Hideo Yagi; Satoshi Yoshihara; Kensuke Ohta; Chihiro Shimazaki; Masayuki Hino; Akifumi Takaori-Kondo; Junya Kuroda; Itaru Matsumura; Yuzuru Kanakura; Shosaku Nomura
    International journal of hematology 112 (4) 435 - 438 2020/09 [Refereed]
     
    We retrospectively analyzed the clinical features and outcomes in a real-world cohort of adolescents and the young adult (AYA) patients (age between 16 and 39 years) with symptomatic multiple myeloma (MM) registered with the Kansai Myeloma Forum. 26 patients had been diagnosed as symptomatic MM out of 3284 patients. The prevalence of AYA-MM was 0.8% in this cohort. 81% of the patients was received stem cell transplantation, which may improve outcome. Anemia and hypercalcemia might be prognostic factors, however International Staging System failed to predict overall survival. Five patients developed late-onset adverse events which were serious and life-threatening. The 5-year overall survival was 71.0%. We need to develop the new strategy to overcome AYA-MM.
  • Yasuhiro Taniguchi; Naoto Takahashi; Masatomo Miura; Chikara Hirase; Sanae Sueda; J Luis Espinoza; Shinya Rai; Shoko Nakayama; Kentaro Serizawa; Takahiro Kumode; Yosaku Watatani; Yasuyoshi Morita; Hirokazu Tanaka; Itaru Matsumura
    Internal medicine (Tokyo, Japan) 59 (21) 2745 - 2749 2020/07 [Refereed]
     
    We recently treated a chronic myeloid leukemia (CML) patient with liver and renal dysfunction, who was undergoing hemodialysis (HD). He was treated with 50 mg dasatinib (DAS) once daily just before HD. The maximum plasma concentration of DAS was 227 ng/mL on a non-HD day and 46.9 ng/mL on a HD day. He was subsequently treated with 200 mg bosutinib (BOS) once daily. The plasma concentration of BOS changed from 74.5 ng/mL before HD to 58.8 ng/mL after HD. Our results indicate that close monitoring of the plasma tyrosine kinase inhibitor concentrations should be considered in CML patients with organ impairment.
  • 中山 聖子; 森田 泰慶; 頼 晋也; 谷口 康博; 谷口 貴英; 田中 宏和; 辰巳 陽一; 芦田 隆司; 松村 到
    日本リンパ網内系学会会誌 (一社)日本リンパ網内系学会 60 83 - 83 1342-9248 2020/07
  • 【血液疾患と消化器系の異常】造血器腫瘍に対する新規分子標的薬による肝障害の留意点
    田中 宏和; 松村 到
    血液内科 (有)科学評論社 80 (6) 849 - 855 2185-582X 2020/06
  • Hiroaki Inoue; Shinya Rai; Hirokazu Tanaka; J. Luis Espinoza; Yosaku Watatani; Takahiro Kumode; Kentaro Serizawa; Shoko Nakayama; Yasuhiro Taniguchi; Yasuyoshi Morita; Yoichi Tatsumi; Takashi Ashida; Itaru Matsumura
    British Journal of Haematology Wiley 191 (2) 243 - 252 0007-1048 2020/05 [Refereed]
     
    Despite duodenal-type follicular lymphoma (DTFL) being morphologically, immunophenotypically and genetically indistinguishable from nodal FL (nFL), this entity typically shows a significantly better prognosis. Here, we analysed the tumour immune microenvironments of diagnostic specimens from patients with DTFL (n = 30), limited-stage FL (LSFL; n = 19) and advanced-stage FL (ASFL; n = 31). The mean number of CD8+ tumour-infiltrating lymphocytes (TILs) in the neoplastic follicles was higher in DTFL (1,827/mm2 ) than in LSFL (1,150/mm2 ) and ASFL (1,188/mm2 ) (P = 0·002, P = 0·002, respectively). In addition, CD8+ PD1-  T cells with non-exhausting phenotype were more abundant in the peripheral blood (PB) of DTFL than in LSFL and ASFL, indicating that DTFL may exhibit a better and longer-lasting T cell-mediated immune response. Moreover, whereas FOXP3+ CTLA-4+ effector regulatory T cells (eTregs) were rarely observed in the neoplastic follicles of DTFL (mean: 12/mm2 ), they were more abundant in LSFL (78/mm2 ) and ASFL (109/mm2 ) (P = 2·80 × 10-5 , P = 4·74 × 10-8 , respectively), and the numbers of eTregs correlated inversely with those of CD8+ TILs (r = -0267; P = 0·018). Furthermore, DTFL showed significantly fewer circulating FOXP3hi CD45RA- CD25hi eTregs (0·146%) than ASFL (0·497%) and healthy controls (0·639%) (P = 0·0003, P = 6·79 × 10-7 , respectively). These results suggest that the augmented anti-tumour immune reactions may contribute to a better prognosis on DTFL.
  • Hirokazu Tanaka
    International Journal of Hematology 111 (4) 494 - 495 0925-5710 2020/04 [Refereed]
  • Hiroaki Inoue; Shinya Rai; Hirokazu Tanaka; J. Luis Espinoza; Maiko Komori-Inoue; Hiroaki Kakutani; Shuji Minamoto; Takahiro Kumode; Shoko Nakayama; Yasuhiro Taniguchi; Yasuyoshi Morita; Takeshi Okuda; Yoichi Tatsumi; Takashi Ashida; Itaru Matsumura
    Viruses 12 (4) 2020/04 [Refereed]
     
    © 2020 by the authors. Aplastic anemia is a rare blood disease characterized by the destruction of the hematopoietic stem cells (HSC) in the bone marrow that, in the majority of cases, is caused by an autoimmune reaction. Patients with aplastic anemia are treated with immunosuppressive drugs and some of them, especially younger individuals with a donor available, can be successfully treated with hematopoietic stem cell transplantation (HSCT). We report here a rare case of post-transplant lymphoproliferative disorder (PTLD) associated with Epstein-Barr virus (EBV) reactivation in a 30-year-old female patient who underwent allogeneic HSCT for severe aplastic anemia. The PTLD, which was diagnosed 230 days after transplantation, was localized exclusively in the central nervous system (specifically in the choroid plexus) and manifested with obvious signs of intracranial hypertension. After receiving three cycles of high dose methotrexate (HD-MTX) combined with rituximab, the patient achieved a complete clinical recovery with normalization of blood cell counts, no evidence of EBV reactivation, and no associated neurotoxicity.
  • Shoko Nakayama; Yasuyoshi Morita; Jorge Luis Espinoza; Shinya Rai; Yasuhiro Taniguchi; Takahide Taniguchi; Yoshiaki Miyake; Hirokazu Tanaka; Takashi Ashida; Itaru Matsumura
    Annals of Hematology 99 (2) 381 - 383 0939-5555 2020/02 [Refereed]
  • Hirokazu Tanaka
    [Rinsho ketsueki] The Japanese journal of clinical hematology 61 (9) 1317 - 1324 2020 
    The treatment paradigm in multiple myeloma (MM) together with the introduction of novel agents have resulted in a considerably improved survival. However, the disease is still considered incurable. One of the factors of its recurrence was that acquired genomic events associated with the progression of MM lead to inter- and intrapatient clonal heterogeneities. Also, just like many other cancers, MM contains cancer stem cells, a rare subpopulation of MM cells that exhibit the capacity for self-renewal and differentiation, but also pronounced drug resistance. Furthermore, a growing body of evidence suggests the role of tumor microenvironment and anti-myeloma immune status in the progression and maintenance of MM. Despite much progress in MM pathology, there are still several issues left unsolved. In this review, we will discuss the recent advances in our understanding of the pathology of MM from the perspective of tumor cell-of-origin and how these advances can lead to more effective therapies targeting MM.
  • Aya Nakaya; Hirokazu Tanaka; Hideo Yagi; Kensuke Ohta; Hirohiko Shibayama; Takae Kohara; Junya Kanda; Maki Shindo; Yuji Shimura; Satoru Kosugi; Toru Kida; Hitomi Kaneko; Kazunori Imada; Takahiro Karasuno; Mitsuhiro Matsuda; Masato Iida; Yoko Adachi; Shin ichi Fuchida; Nobuhiko Uoshima; Hitoji Uchiyama; Ryoichi Takahashi; Toshimitsu Matsui; Katsuya Wada; Miki Kiyota; Chihiro Shimazaki; Masayuki Hino; Junya Kuroda; Yuzuru Kanakura; Akifumi Takaori-Kondo; Shosaku Nomura; Itaru Matsumura
    International Journal of Hematology 0925-5710 2020 [Refereed]
     
    © 2020, Japanese Society of Hematology. We retrospectively analyzed 51 patients with solitary plasmacytoma diagnosed from October 2002 to September 2018 from a cohort of 3575 patients with plasma cell dyscrasias registered in the Kansai Myeloma Forum. Twenty-seven patients had solitary bone plasmacytoma (SBP) and 24 had extramedullary plasmacytoma (EMP), with prevalence of 0.8% and 0.7%, respectively. The most frequent M protein was IgG (40%) in SBP, whereas non-secretory proteins were most frequent (50%) in EMP. Five-year overall survival was 78.2% in SBP and 80.8% in EMP (P = 0.894). Among patients with SBP, 44% progressed to MM with a median time of 10.5 months (2.4–93.3 months), whereas 8% of EMP patients progressed to MM with a median time of 18.6 months (13.0–24.2 months). The most frequent treatment was radiotherapy (41%) or observation (41%) in SBP, and chemotherapy (54%) in EMP. No statistically significant difference was observed upon univariate analysis of prognostic factors including age, sex, performance status, and IgG M protein. Our results suggest that there are biological differences between SBP and EMP in real-world settings.
  • Takahiro Kumode; Shinya Rai; Hirokazu Tanaka; J Luis Espinoza; Hiroaki Kakutani; Yosaku Watatani; Shuji Minamoto; Yasuhiro Taniguchi; Shoko Nakayama; Yasuyoshi Morita; Takashi Ashida; Itaru Matsumura
    Leukemia research reports 14 100219 - 100219 2020 [Refereed]
     
    We report a case with extramedullary tumors affecting the supraclavicular region that presented as a relapse of acute myeloid leukemia (AML) with FLT3-ITD mutation after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Treatment with gilteritinib resulted in remarkable response with disappearance of both the medullary and extramedullary tumors. Subsequently, a 2nd allo-HSCT was performed in an attempt to cure his AML and complete molecular response has been sustained with gilteritinib resumption without worsening GVHD. Targeted therapy with gilteritinib for medullary and extramedullary relapse of FLT3-ITD AML could be effective and suitable as a bridging therapy for allo-HSCT.
  • 田中 宏和; 松村 到
    血液内科 (有)科学評論社 79 (5) 663 - 668 2185-582X 2019/11
  • Takaya Yamashita; Kazuhiro Ikegame; Fumiko Ito; Takahiro Kobayashi; Miho Nara; Naohito Fujishima; Akira Anbai; Takayuki Inoue; Katsuji Kaida; Hidenori Tanaka; Naoto Takahashi
    Bone marrow transplantation 54 (10) 1713 - 1716 0268-3369 2019/10 [Refereed]
  • 田中 宏和; 松村 到
    腫瘍内科 (有)科学評論社 24 (3) 276 - 284 1881-6568 2019/09
  • 岩田吉生; 森田泰慶; 辻潔; 頼晋也; 田崎貴之; 井上宏昭; 谷口康博; 藤本昂; 田中宏和; 芦田隆司; 加藤天美; 松村到
    PNH Frontier (株)メディカルレビュー社 (6) 46 - 49 2188-4552 2019/07 
    症例は35歳女性で、17歳時に再生不良性貧血-発作性夜間ヘモグロビン尿症(PNH)症候群と診断され、無治療で経過観察されていた。今回、感冒症状が出現し、全身倦怠感・褐色尿などの増悪を認めていた。自室で昏睡状態になっているのを家人が発見し救急要請された。頭部CTでは脳の正中偏移を伴う左前頭葉脳浮腫所見を認め、CT Venographyで上矢状静脈洞の描出欠損を認めた。以上より、上矢状静脈洞血栓症による脳梗塞に起因する意識障害と診断され緊急入院となった。第1病日夜間に意識レベル低下、瞳孔不同の症状が出現し、頭部CTで左前頭葉脳浮腫の増悪を認めたため、緊急開頭減圧術を実施した。さらに、術後侵襲による補体活性化と溶血再燃を抑制する目的で、術後第2病日に髄膜炎菌ワクチンとエクリズマブ投与を開始した。ワルファリンとエクリズマブ投与を継続し、溶血発作の再燃を認めることはなく、第53病日に退院となった。
  • Kamura K; Omori M; Kurokawa M; Tanaka H
    Waste management (New York, N.Y.) 93 122 - 129 0956-053X 2019/06 [Refereed]
  • 田中 宏和; 松村 到
    血液内科 (有)科学評論社 78 (5) 579 - 586 2185-582X 2019/05
  • 井上 宏昭; 頼 晋也; 口分田 貴裕; 芹澤 憲太郎; 谷口 康博; 中山 聖子; 森田 泰慶; Luis Espinoza J.; 田中 宏和; 辰巳 陽一; 芦田 隆司; 松村 到
    日本リンパ網内系学会会誌 (一社)日本リンパ網内系学会 59 119 - 119 1342-9248 2019/05
  • 中山 聖子; 松田 光弘; 森田 泰慶; 頼 晋也; 谷口 康博; 井上 宏昭; 大山 泰世; 谷口 貴英; 三宅 義昭; 足立 達哉; 末田 早苗; Espinoza J. Luis; 田中 宏和; 辰巳 陽一; 芦田 隆司; 松村 到
    日本リンパ網内系学会会誌 (一社)日本リンパ網内系学会 59 126 - 126 1342-9248 2019/05
  • 三宅 義昭; 頼 晋也; 井上 宏昭; 口分田 貴裕; 谷口 康博; 中山 聖子; 森田 泰慶; Espinoza J.L.; 田中 宏和; 辰巳 陽一; 芦田 隆司; 松村 到
    日本リンパ網内系学会会誌 (一社)日本リンパ網内系学会 59 129 - 129 1342-9248 2019/05
  • 谷口 貴英; 中山 聖子; 森田 泰慶; 頼 晋也; 平瀬 主税; 谷口 康博; 井上 宏昭; 大山 泰世; 三宅 義昭; Espinoza J Luis; 田中 宏和; 辰巳 陽一; 芦田 隆司; 松村 到
    日本リンパ網内系学会会誌 (一社)日本リンパ網内系学会 59 129 - 129 1342-9248 2019/05
  • 田中 宏和; 松村 到
    血液内科 (有)科学評論社 78 (5) 579 - 586 2185-582X 2019/05
  • Hirokazu Tanaka; J Luis Espinoza; Ryosuke Fujiwara; Shinya Rai; Yasuyoshi Morita; Takashi Ashida; Yuzuru Kanakura; Itaru Matsumura
    Cells 8 (3) 2019/03 [Refereed]
     
    Iron overload is the accumulation of excess iron in the body that may occur as a result of various genetic disorders or as a consequence of repeated blood transfusions. The surplus iron is then stored in the liver, pancreas, heart and other organs, which may lead to chronic liver disease or cirrhosis, diabetes and heart disease, respectively. In addition, excessive iron may impair hematopoiesis, although the mechanisms of this deleterious effect is not entirely known. In this study, we found that ferrous ammonium sulfate (FeAS), induced growth arrest and apoptosis in immature hematopoietic cells, which was mediated via reactive oxygen species (ROS) activation of p38MAPK and JNK pathways. In in vitro hematopoiesis derived from embryonic stem cells (ES cells), FeAS enhanced the development of dysplastic erythroblasts but inhibited their terminal differentiation; in contrast, it had little effect on the development of granulocytes, megakaryocytes, and B lymphocytes. In addition to its directs effects on hematopoietic cells, iron overload altered the expression of several adhesion molecules on stromal cells and impaired the cytokine production profile of these cells. Therefore, excessive iron would affect whole hematopoiesis by inflicting vicious effects on both immature hematopoietic cells and stromal cells.
  • 谷口貴英; 中山聖子; 森田泰慶; 頼晋也; 大山泰世; 三宅義昭; 田中宏和; 辰巳陽一; 芦田隆司; 松村到
    臨床血液 (一社)日本血液学会-東京事務局 60 (1) 65‐66 - 66 0485-1439 2019/01
  • Shoko Nakayama; Yasuyoshi Morita; Jorge Luis Espinoza; Shinya Rai; Yasuyo Oyama; Takahide Taniguchi; Yoshiaki Miyake; Hirokazu Tanaka; Itaru Matsumura
    Leukemia and Lymphoma 1 - 3 1042-8194 2019 [Refereed]
  • Shoko Nakayama; Takahide Taniguchi; Hirokazu Tanaka; Jorge L. Espinoza; Shinya Rai; Itaru Matsumura
    British Journal of Haematology 184 (2) 122 - 122 0007-1048 2019/01 [Refereed]
  • Takabayashi K; Tanaka H; Sakakibara K
    Sensors (Basel, Switzerland) 19 (1) 2018/12 [Refereed]
  • 末梢血幹細胞採取前のCD34細胞数測定の有用性
    山田 枝里佳; 斉藤 花往里; 藤本 昂; 角谷 宏明; 岩田 吉生; 谷口 貴英; 源 周治; 大山 泰世; 口分田 貴裕; 井上 宏昭; 芹澤 憲太郎; 谷口 康博; 頼 晋也; 平瀬 主税; 森田 泰慶; 田中 宏和; 岡野 意浩; 坂田 尚己; 芦田 隆司; 松村 到
    日本アフェレシス学会雑誌 (一社)日本アフェレシス学会 37 (Suppl.) 131 - 131 1340-5888 2018/10
  • Shinya Rai; Hirokazu Tanaka; Ko Fujimoto; Takahiro Kumode; Hiroaki Inoue; Yasuhiro Taniguchi; Yasuyoshi Morita; J. Luis Espinoza; Yoichi Tatsumi; Takashi Ashida; Ryota Matsuoka; Yukie Yara Kikuti; Naoya Nakamura; Itaru Matsumura
    Cancers 10 (9) 2018/09 [Refereed]
     
    © 2018 by the authors. Licensee MDPI, Basel, Switzerland. A 62-year-old male was diagnosed with chronic lymphocytic leukemia (CLL) and treated with a fludarabine-containing regimen which maintained the disease in a partial response. Nine years after diagnosis, a rapidly growing systemic lymphadenopathy was observed, and a biopsy specimen revealed the presence of typical Hodgkin/Reed-Sternberg (HRS) cells, surrounded by T-lymphocytes and CLL cells. Sequencing analysis of the germline complementary determining region 3 (CDR3) region of the immunoglobulin heavy chain (IGH) gene showed that the Hodgkin/Reed-Sternberg cells were clonally unrelated to the preexisting CLL cells and the HRS cells were composed of five different clones, leading to the molecular diagnosis of de novo lymphocyte-rich classic Hodgkin lymphoproliferative diseases (LPDs) with small lymphocytic lymphoma (SLL). As the initial treatment was neither effective for classic Hodgkin LPDs nor for SLL, Bendamustine, Rituximab (BR) was started and complete remission was achieved, which has continued for more than one year so far. BR may be a good therapeutic option for both entities without causing hematological toxicity.
  • 異常なRTKの細胞内輸送阻害は急性骨髄性白血病における有望な治療標的である(Intracellular trafficking of mutated RTKs shows promising therapeutic target against AML)
    頼 晋也; 田中 宏和; 鈴木 麻衣; Espinoza Luis; 谷村 朗; 森田 泰慶; 辰巳 陽一; 横田 貴史; 織谷 健司; 渡邊 俊雄; 金倉 譲; 松村 到
    臨床血液 (一社)日本血液学会-東京事務局 59 (9) 1486 - 1486 0485-1439 2018/09
  • BCR-ABL陰性骨髄増殖性腫瘍においてTET2変異は生存に対する予後不良因子である(TET2 mutation is a poor prognostic factor for survival in BCR-ABL-negative MPN patients)
    谷口 康博; 田中 宏和; 藤原 亮介; 森田 泰慶; 花本 仁; 辰巳 陽一; 芦田 隆司; 松村 到
    臨床血液 (一社)日本血液学会-東京事務局 59 (9) 1529 - 1529 0485-1439 2018/09
  • CLEC-2の発現は巨核球にバイアスした長期骨髄再建能を有する造血幹細胞集団を規定する(CLEC-2 identifies a functionally distinct subpopulation of megakaryocyte-biased HSCs)
    口分田 貴裕; 田中 宏和; Espinoza J. Luis; 岩田 吉生; 佐野 圭吾; 芹澤 憲太郎; 谷口 康博; 頼 晋也; 森田 泰慶; 辰巳 陽一; 芦田 隆司; 松村 到
    臨床血液 (一社)日本血液学会-東京事務局 59 (9) 1572 - 1572 0485-1439 2018/09
  • 十二指腸型濾胞性リンパ腫は、抗腫瘍免疫により良好な予後を示す(Duodenal-type follicular lymphoma exhibits good prognosis through the increased anti-tumor immunity)
    井上 宏昭; 頼 晋也; 口分田 貴裕; 芹澤 憲太郎; 谷口 康博; 中山 聖子; 森田 泰慶; ルイス・エスピノザ; 田中 宏和; 辰巳 陽一; 芦田 隆司; 松村 到
    臨床血液 (一社)日本血液学会-東京事務局 59 (9) 1592 - 1592 0485-1439 2018/09
  • CD34陽性ヒト骨髄腫幹細胞の同定と特性解析(Identification and characterization of CD34+ myeloma cell population as myeloma-initiating cells)
    芹澤 憲太郎; 田中 宏和; 福井 彩乃; 藤原 亮介; 佐野 圭吾; 口分田 貴裕; 谷口 康博; 森田 泰慶; ルイス・エスピノザ; 辰巳 陽一; 芦田 隆司; 松村 到
    臨床血液 (一社)日本血液学会-東京事務局 59 (9) 1605 - 1605 0485-1439 2018/09
  • 骨髄異形成症候群に合併したSweet病に対するアザシチジンの免疫学的効果(Immunological effects of azacitidin on Sweet's disease associated with myelodysplastic syndromes)
    谷口 貴英; 芹澤 憲太郎; 田中 宏和; 森田 泰慶; 谷口 康博; 辰巳 陽一; 芦田 隆司; 松村 到
    臨床血液 (一社)日本血液学会-東京事務局 59 (9) 1686 - 1686 0485-1439 2018/09
  • 脳静脈洞血栓症を合併し、開頭減圧術・術後エクリズマブ投与が有効であったPNHの一例(Post-operative treatment with eculizumab for PNH presenting as cerebral venous sinus thrombosis)
    岩田 吉生; 森田 泰慶; 辻 潔; 頼 晋也; 田崎 貴之; 井上 宏昭; 谷口 康博; 藤本 昂; 田中 宏和; 芦田 隆司; 加藤 天美; 松村 到
    臨床血液 (一社)日本血液学会-東京事務局 59 (9) 1765 - 1765 0485-1439 2018/09
  • Kentaro Serizawa; Hirokazu Tanaka; Yasuyoshi Morita; Takahide Taniguchi; Takashi Ashida; Itaru Matsumura
    Frontiers in Oncology 8 (JUN) 204 - 204 2018/06 [Refereed]
     
    © 2018 Serizawa, Tanaka, Morita, Taniguchi, Ashida and Matsumura. Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal disorders of hematopoietic stem cells, characterized by dysplastic hematopoiesis and dysregulated immune system resulting in various clinical conditions. Paraneoplastic inflammatory syndromes, which are well known to be associated with MDS, show response to immune-modulated therapy and often disappear during the course of hematologic management. Azacitidine (5-Aza) was shown to prolong survival of high-risk MDS patients, however, the effects of 5-Aza on paraneoplastic inflammation in MDS have yet to be elucidated. 5-Aza was administered to a 60-year-old man with MDS accompanying Sweet's syndrome at a dose of 75 mg/m2/daily subcutaneously for 7 days every 28 days. 5-Aza was not only effective in controlling systemic symptoms caused by paraneoplastic inflammation, but hematologic improvements were also observed after four cycles of the 5-Aza treatment. Immune profiling in peripheral blood before and after 5-Aza treatment revealed that the effector and naive regulatory T cells in lymphocytes drastically increased after the 5-Aza treatment, i.e., 5-Aza might induce a shift in lymphocytic populations toward immunosuppression in this patient. Our results raised the immune-mediated effect of 5-Aza on both dysplastic hematopoiesis and paraneoplastic inflammation in myelodyplastic syndromes.
  • Okada M; Imagawa J; Tanaka H; Nakamae H; Hino M; Murai K; Ishida Y; Kumagai T; Sato S; Ohashi K; Sakamaki H; Wakita H; Uoshima N; Nakagawa Y; Minami Y; Ogasawara M; Takeoka T; Akasaka H; Utsumi T; Uike N; Sato T; Ando S; Usuki K; Mizuta S; Hashino S; Nomura T; Shikami M; Fukutani H; Ohe Y; Kosugi H; Shibayama H; Maeda Y; Fukushima T; Yamazaki H; Tsubaki K; Kukita T; Adachi Y; Nataduka T; Sakoda H; Yokoyama H; Okamoto T; Shirasugi Y; Onishi Y; Nohgawa M; Yoshihara S; Morita S; Sakamoto J; Kimura S
    Clinical Lymphoma Myeloma and Leukemia 18 (5) 353 - 360 2018/05 [Refereed]
  • Yayoi Matsumura-Kimoto; Junya Kuroda; Hitomi Kaneko; Yuri Kamitsuji; Shin ichi Fuchida; Aya Nakaya; Hirohiko Shibayama; Nobuhiko Uoshima; Isao Yokota; Hitoji Uchiyama; Hideo Yagi; Satoru Kosugi; Toshimitsu Matsui; Jun Ishikawa; Mitsuhiro Matsuda; Kensuke Ohta; Masato Iida; Hirokazu Tanaka; Masayuki Kobayashi; Katsuya Wada; Chihiro Shimazaki; Shosaku Nomura; Kazunori Imada; Masayuki Hino; Itaru Matsumura; Yuzuru Kanakura; Akifumi Takaori-Kondo
    International Journal of Hematology 107 (5) 541 - 550 0925-5710 2018/05 [Refereed]
     
    © 2018, The Japanese Society of Hematology. Determinants of the efficacy and safety of pomalidomide (POM) monotherapy or POM plus dexamethasone (DEX) (POM/DEX) for relapsed and refractory multiple myeloma (RRMM) were examined retrospectively in a real-world clinical practice setting in Japan. The subjects were 108 patients registered with the Kansai Myeloma Forum, who were treated with either POM or POM/DEX. Of these, 79 (73%), 73 (68%), and 58 (54%) were resistant to bortezomib (BTZ), lenalidomide (LEN), and both BTZ and LEN, respectively. The median overall survival (OS) was not reached. The median time to treatment failure (TTF) was 4.4 months. The best response was recorded in 96 patients, with a 31% overall response rate (ORR) and a 79% rate of achieving at least stable disease. Number of pre-POM regimens ≥ 5, non-IgG-type M-protein, and time from initial therapy to POM or POM/DEX therapy < 2 years were associated with shorter TTF and OS. Frequent (> 10%) severe adverse events included neutropenia (55.1%), thrombocytopenia (33.7%), anemia (30.6%), febrile neutropenia (12.2%), fatigue (11.2%), and anorexia (10.2%). In conclusion, POM and POM/DEX showed substantial efficacy against RRMM, but new combination therapies with POM are needed to improve efficacy further without causing hematologic toxicities.
  • 難治性血栓症を伴うI型クリオグロブリン血症を合併したリンパ形質細胞性リンパ腫の1例
    國田 裕貴; 口分田 貴裕; 波江野 高大; 森田 泰慶; 嶋田 高広; 田中 宏和; 辰巳 陽一; 芦田 隆司; 松村 到
    臨床血液 (一社)日本血液学会-東京事務局 59 (2) 239 - 240 0485-1439 2018/02
  • 複数の免疫異常を合併した脾辺縁帯リンパ腫の1例
    三宅 義昭; 口分田 貴裕; 波江野 高大; 森田 泰慶; 嶋田 高広; 田中 宏和; 辰巳 陽一; 芦田 隆司; 松村 到
    臨床血液 (一社)日本血液学会-東京事務局 59 (2) 240 - 240 0485-1439 2018/02
  • J. Luis Espinoza; Ayumi Matsumoto; Hirokazu Tanaka; Itaru Matsumura
    Cancer Letters Elsevier Ireland Ltd 414 147 - 152 0304-3835 2018/02 [Refereed]
     
    © 2017 Elsevier B.V. The complex diversity of nonpathogenic microbes that colonize the human body, known as microbiota, exert considerable effects on physiological homeostasis, and immune regulation. Helicobacter pylori (H. pylori) is a bacterium that frequently colonizes human stomach and is a major pathogenic agent for peptic ulcer diseases, gastric cancer, and mucosa-associated lymphoid tissue (MALT) lymphoma. Due to its acidic pH and peristaltic movements, the stomach has been considered a hostile environment for most microorganisms, however various commensal microorganisms are capable of colonizing the stomach to form a stomach niche. Recent pieces of evidence indicate that commensal gastric microbes or their metabolites influence the capability of H. pylori to colonize the stomach and directly modulate its pathogenicity and carcinogenic potential. In this article, we present an overview of recent advances in the understanding of H. pylori-commensal interactions in the pathogenesis and clinical evolution of H. pylori-associated gastric malignancies.
  • Junichi Miyatake; Hiroaki Inoue; Kentarou Serizawa; Yasuyoshi Morita; J. L. Espinoza; Hirokazu Tanaka; Takahiro Shimada; Yoichi Tatsumi; Takashi Ashida; Itaru Matsumura
    Internal Medicine 57 (10) 1445 - 1453 0918-2918 2018 [Refereed]
     
    © 2018 The Japanese Society of Internal Medicine. Patients with mycosis fungoides (MF), the most common subtype of primary cutaneous T-cell lymphoma, have an increased risk of developing secondary malignancies. We herein report two rare cases of MF concurring with diffuse large B cell lymphoma (B lymphoid lineage) and acute myeloid leukemia (myeloid lineage) in two otherwise healthy elderly patients. Potential etiologic factors, including the impact of the therapy-associated inflammatory response on the development of secondary tumors in patients with MF, are discussed. Further clinical, experimental and genetic studies are needed to elucidate possible physiopathogenic associations among the three concurrent malignancies occurring in the cases presented here.
  • Aya Nakaya; Hideo Yagi; Hitomi Kaneko; Satoru Kosugi; Toru Kida; Yoko Adachi; Hirohiko Shibayama; Takae Kohara; Yuri Kamitsuji; Shin ichi Fuchida; Nobuhiko Uoshima; Eri Kawata; Hitoji Uchiyama; Yuji Shimura; Takayuki Takahashi; Fumiaki Urase; Kensuke Ohta; Tsuneyoshi Hamada; Kazue Miyamoto; Masayuki Kobayashi; Maki Shindo; Hirokazu Tanaka; Chihiro Shimazaki; Masayuki Hino; Junya Kuroda; Yuzuru Kanakura; Akifumi Takaoari-Kondo; Shosaku Nomura; Itaru Matsumura
    Leukemia Research Reports 10 7 - 10 2213-0489 2018/01 [Refereed]
     
    © 2018 The Authors We retrospectively analyzed twenty-six patients with primary plasma cell leukemia (pPCL) registered from May 2005 until April 2015 by the Kansai Myeloma Forum. Twenty patients received novel agents (bortezomib or lenalidomide), and their median survival of was 34 months. The median survival of patients who underwent autologous stem cell transplantation (SCT) was 40 months, those undergoing allogeneic SCT 55 months, and those undergoing both types of SCT (auto–allo) 61 months; whereas for those who did not undergo SCT it was 28 months (p = 0.845). The only statistically significant risk factor identified by multivariate analysis was hypercalcemia.
  • Shinya Rai; J Luis Espinoza; Yasuyoshi Morita; Hirokazu Tanaka; Itaru Matsumura
    Frontiers in immunology 9 3031 - 3031 2018 [Refereed]
     
    Myelodysplastic syndromes (MDS) are a heterogeneous group clonal disorders of hematopoietic stem cells (HSC) characterized by ineffective hematopoiesis that lead to variable grades of impaired blood cell production. Chromosomal aberrations are often detected in MDS patients and thus cytogenetic analysis is useful for the diagnosis of these disorders. Common recurring chromosomal defects, such as the -5/5q- and -7/7q- are relatively well characterized cytogenetic abnormalities in MDS, however, the biological significance of uncommon cytogenetic alterations is unknown. We report here, two cases of peripheral blood and bone marrow hypereosinophilia in patients with MDS harboring the unbalanced translocation der(1;7)(q10;p10), a poorly characterized cytogenetic abnormality that is found in certain myeloid malignancies, including MDS. The patients reported here presented hypereosinophilia that was refractory to steroids and cytotoxic therapy, leading to severe target tissue damage that ultimately resulted in fatal end-organ failure. Potential roles of the der(1;7)(q10;p10) aberrations in the pathogenesis of aggressive eosinophilia and disease prognosis are discussed here.
  • Tanaka H; Nakatani E; Fukutomi Y; Sekiya K; Kaneda H; Iikura M; Yoshida M; Takahashi K; Tomii K; Nishikawa M; Kaneko N; Sugino Y; Shinkai M; Ueda T; Tanikawa Y; Shirai T; Hirabayashi M; Aoki T; Kato T; Iizuka K; Fujii M; Taniguchi M
    Allergy 0105-4538 2017/12 [Refereed]
  • 芹澤憲太郎; 芦田隆司; 谷口貴英; 谷口康博; 森田泰慶; 田中宏和; 嶋田高広; 辰巳陽一; 松村到
    臨床血液 (一社)日本血液学会-東京事務局 58 (12) 2386‐2391(J‐STAGE) - 2391 0485-1439 2017/12 [Refereed]
     
    急性骨髄性白血病に対する同種骨髄移植後に一旦造血機能の回復を認めたものの汎血球減少を来し、二次性生着不全と判断してドナーリンパ球輸注(donor lymphocyte infusion,DLI)を施行したところ著効を示した症例を経験したので報告する。症例は64歳女性。急性骨髄性白血病の部分寛解に対して非血縁者間同種骨髄移植を施行した。速やかに生着し、complete remission with incomplete blood count recovery(CRi)に到達したが、day 110から汎血球減少症が出現した。血液検査および骨髄穿刺では、再発や血球貪食症候群は認めないものの、キメリズム解析でドナー比率が経時的に低下したため、二次性生着不全と診断した。Granulocyte-colony stimulating factor(G-CSF)の投与と輸血にて経過観察したが、造血の改善は認めなかった。患者が再移植を希望しなかったため、DLIを施行した(CD3陽性細胞:1.0×107/kg、単回投与)ところ、有害事象を認めることなく、血球は速やかに改善した。(著者抄録)
  • Yasuhiro Taniguchi; Hirokazu Tanaka; Espinoza J. Luis; Kazuko Sakai; Takahiro Kumode; Keigo Sano; Kentarou Serizawa; Shinya Rai; Yasuyoshi Morita; Hitoshi Hanamoto; Kazuo Tsubaki; Kazuto Nishio; Itaru Matsumura
    International Journal of Hematology SPRINGER JAPAN KK 106 (5) 691 - 703 0925-5710 2017/11 [Refereed]
     
    © 2017, The Japanese Society of Hematology. Myeloproliferative neoplasms (MPNs), including polycythemia vera and essential thrombocythemia, are frequently associated with thrombotic complications. Prevention of thrombotic events is thus a primary aim of the current treatment for these disorders. Although it is known that microparticles (MPs), which are small vesicles released from cell membranes and circulate in the blood, directly contribute to thrombosis via their procoagulant activity, potential associations between plasma levels of MPs and the risk of thrombotic events in MPNs have not been reported. In the present study, we characterized plasma levels of MPs and assessed their potential association with the occurrence of thrombotic events in 59 patients with MPNs. Plasma levels of procoagulant MPs expressing tissue factor (TF+ MPs) were significantly higher in patients suffering thrombotic events than in patients without such events (median/μl plasma: 33.8 vs 47.2, p = 0.02). Among patients who developed thrombotic events, irrespective of patients’ blood counts, TF+ MP were significantly higher in patients without cytoreductive therapy than in those receiving cytoreductive therapy (101.2 vs. 42.5, p < 0.001). These results suggest that elevated levels of TF+ MP may be considered as a novel surrogate marker for thrombotic events in MPN patients. Further studies are needed to clarify the mechanism involved.
  • 田中宏和; 松村到
    月刊血液内科 科学評論社 75 (2) 163‐168 - 136 2185-582X 2017/08
  • T. Kumode; H. Tanaka; R. Fujiwara; K. Sano; K. Serizawa; Y. Taniguchi; S. Rai; I. Matsumura
    HAEMATOLOGICA FERRATA STORTI FOUNDATION 102 452 - 453 0390-6078 2017/06
  • Hiroaki Inoue; Yasuyoshi Morita; Shinya Rai; Hiroaki Kakutani; Yasuyo Ohyama; Yasuhiro Taniguchi; Hirokazu Tanaka; Takahiro Shimada; Yoichi Tatsumi; Takashi Ashida; Itaru Matsumura
    [Rinsho ketsueki] The Japanese journal of clinical hematology 58 (2) 138 - 142 0485-1439 2017 [Refereed]
     
    Immunosuppressive therapy after solid organ transplantation is known to be a risk factor for the development of myelodysplastic syndromes (MDS). Herein, we report 2 patients, both of whom developed low-risk MDS after solid organ transplantation and were successfully treated with azacitidine (AZA). The 1st case was a 74-year-old man who had received liver transplantation. The initial immunosuppressive therapy consisted of cyclosporine and prednisolone. Nine years after transplantation, he was diagnosed as having MDS (RCMD). The 2nd case was a 47-year-old woman who had received cadaveric renal transplantation. The initial immunosuppressive therapy was comprised of cyclosporine, azathioprine, and prednisolone. Twenty-seven years after transplantation, she developed MDS (RA). Both patients received 75 mg/m2 AZA once daily for five consecutive days on a 28-day cycle. After 2 courses of therapy, both patients achieved hematological improvement (IWG 2006 criteria) without severe (grade 3/4) non-hematological adverse events. Moreover, AZA did not affect the status of organ transplantation in terms of engraftment and function of the graft. In conclusion, AZA would be a safe and effective agent for patients with MDS after solid organ transplantation. However, long-term follow-up is needed to confirm the safety and efficacy of AZA for patients undergoing solid organ transplantations.
  • Hiroaki Inoue; Yasuyoshi Morita; Shinya Rai; Hiroaki Kakutani; Yasuyo Ohyama; Yasuhiro Taniguchi; Hirokazu Tanaka; Takahiro Shimada; Yoichi Tatsumi; Takashi Ashida; Itaru Matsumura
    [Rinsho ketsueki] The Japanese journal of clinical hematology (一社)日本血液学会-東京事務局 58 (2) 138 - 142 0485-1439 2017 
    Immunosuppressive therapy after solid organ transplantation is known to be a risk factor for the development of myelodysplastic syndromes (MDS). Herein, we report 2 patients, both of whom developed low-risk MDS after solid organ transplantation and were successfully treated with azacitidine (AZA). The 1st case was a 74-year-old man who had received liver transplantation. The initial immunosuppressive therapy consisted of cyclosporine and prednisolone. Nine years after transplantation, he was diagnosed as having MDS (RCMD). The 2nd case was a 47-year-old woman who had received cadaveric renal transplantation. The initial immunosuppressive therapy was comprised of cyclosporine, azathioprine, and prednisolone. Twenty-seven years after transplantation, she developed MDS (RA). Both patients received 75 mg/m2 AZA once daily for five consecutive days on a 28-day cycle. After 2 courses of therapy, both patients achieved hematological improvement (IWG 2006 criteria) without severe (grade 3/4) non-hematological adverse events. Moreover, AZA did not affect the status of organ transplantation in terms of engraftment and function of the graft. In conclusion, AZA would be a safe and effective agent for patients with MDS after solid organ transplantation. However, long-term follow-up is needed to confirm the safety and efficacy of AZA for patients undergoing solid organ transplantations.
  • 田中宏和; 松村到
    日本臨床 74 526‐530  0047-1852 2016/12
  • 小杉 智; 柴山 浩彦; 中谷 英仁; 木田 亨; 太田 健介; 金子 仁臣; 八木 秀男; 田中 宏和; 淵田 真一; 中谷 綾; 小林 正行; 黒田 純也; 上辻 由里; 魚嶋 伸彦; 足立 陽子; 通堂 満; 島崎 千尋; 野村 昌作; 日野 雅之; 松村 到; 谷脇 雅史; 金倉 譲; 高折 晃史
    臨床血液 (一社)日本血液学会-東京事務局 57 (7) 839 - 847 0485-1439 2016/07 [Refereed]
     
    新規薬剤により骨髄腫患者の生存が延長すると共に,二次がん発生が問題になっている。今回,関西骨髄腫フォーラム(KMF)データベースを用い,2012年11月〜2015年3月に登録された骨髄腫および関連疾患1571例について二次がん発生を解析した。観察期間(中央値31ヵ月)内に血液腫瘍が10例,固形がんが36例に発生していた(5年累積発生率:血液腫瘍1.0%,固形がん3.7%)。未治療の無症候性骨髄腫およびMGUS症例では,固形がん発生を認める一方で血液腫瘍発生は認めなかったが,累積発生率においては治療例との間に有意差を認めなかった。一方,melphalan,bortezomib,lenalidomideおよびthalidomideの4剤それぞれの投与歴を見た場合,血液腫瘍発生への影響は統計学的に認められない一方,レナリドマイド投与歴のある患者で固形がん発生が多く認められた。より詳細な検討には,本データベースへのさらなる症例数の蓄積と,長期の観察が必要と考える。(著者抄録)
  • Satoru Kosugi; Hirohiko Shibayama; Eiji Nakatani; Toru Kida; Kensuke Ohta; Hidemi Kaneko; Hideo Yagi; Hirokazu Tanaka; Shin Ichi Fuchida; Aya Nakaya; Masayuki Kobayashi; Junya Kuroda; Yuri Kamitsuji; Nobuhiko Uoshima; Yoko Adachi; Mitsuru Tsudo; Chihiro Shimazaki; Shosaku Nomura; Masayuki Hino; Itaru Matsumura; Masashi Taniwaki; Yuzuru Kanakura; Akifumi Takaori-Kondo
    [Rinsho ketsueki] The Japanese journal of clinical hematology The Japanese Society of Hematology 57 (7) 839 - 847 0485-1439 2016/07 [Refereed]
     
    The incidence of second primary malignancies (SPMs) in Japanese patients with myeloma or myeloma-related diseases was studied by using the Kansai Myeloma Forum (KMF) database registered from November 2012 to March 2015. We studied 1,571 cases. Hematologic malignancies were documented in 10 patients, and solid tumors in 36 during this period. The cumulative 5-year incidence was estimated to be 1.0% for hematological malignancies and 3.7% for solid tumors. In the patients with smoldering myeloma or MGUS without treatment, solid tumors but not hematologic malignancies developed, though the cumulative incidence of each malignancy did not differ significantly from that in patients receiving treatment. Although statistical analysis showed that treatment with melphalan, bortezomib, lenalidomide, or thalidomide had no effect on the occurrence of hematological malignancies, lenalidomide administration was more frequent in the patients with solid tumors. To evaluate the SPMs in myeloma or myeloma-related diseases more accurately, accumulation of a larger number of patients and longer observation are needed.
  • 芹澤 憲太郎; 森田 泰慶; 口分田 貴裕; 田中 宏和; 山田 枝里佳; 芦田 隆司; 松村 到
    日本輸血細胞治療学会誌 (一社)日本輸血・細胞治療学会 62 (2) 272 - 272 1881-3011 2016/04
  • Tomohiko Ishibashi; Takafumi Yokota; Hirokazu Tanaka; Michiko Ichii; Takao Sudo; Yusuke Satoh; Yukiko Doi; Tomoaki Ueda; Akira Tanimura; Yuri Hamanaka; Sachiko Ezoe; Hirohiko Shibayama; Kenji Oritani; Yuzuru Kanakura
    Experimental Hematology ELSEVIER SCIENCE INC 44 (4) 269 - 281.e1 0301-472X 2016/04 [Refereed]
     
    © 2016 ISEH - International Society for Experimental Hematology. Reliable markers are essential to increase our understanding of the biological features of human hematopoietic stem cells and to facilitate the application of hematopoietic stem cells in the field of transplantation and regenerative medicine. We previously identified endothelial cell-selective adhesion molecule (ESAM) as a novel functional marker of hematopoietic stem cells in mice. Here, we found that ESAM can also be used to purify human hematopoietic stem cells from all the currently available sources (adult bone marrow, mobilized peripheral blood, and cord blood). Multipotent colony-forming units and long-term hematopoietic-reconstituting cells in immunodeficient mice were found exclusively in the ESAMHigh fraction of CD34+CD38- cells. The CD34+CD38- fraction of cord blood and collagenase-treated bone marrow contained cells exhibiting extremely high expression of ESAM; these cells are likely to be related to the endothelial lineage. Leukemia cell lines of erythroid and megakaryocyte origin, but not those of myeloid or lymphoid descent, were ESAM positive. However, high ESAM expression was observed in some primary acute myeloid leukemia cells. Furthermore, KG-1a myeloid leukemia cells switched from ESAM negative to ESAM positive with repeated leukemia reconstitution in vivo. Thus, ESAM is a useful marker for studying both human hematopoietic stem cells and leukemia cells.
  • 田中宏和; 松村到
    月刊腫瘍内科 (有)科学評論社 16 (5) 467 - 473 1881-6568 2015/11
  • Kentaro Serizawa; Yasuyoshi Morita; Yosaku Watatani; Yasuyo Oyama; Chikara Hirase; Hirokazu Tanaka; Junichi Miyatake; Yoichi Tatsumi; Takashi Ashida; Itaru Matsumura
    ANNALS OF ONCOLOGY OXFORD UNIV PRESS 26 108 - 108 0923-7534 2015/11 [Refereed]
  • Mami Sumiyoshi; Narumi Masuda; Nobuhiro Tanuma; Honami Ogoh; Eri Imai; Mizuki Otsuka; Natsuki Hayakawa; Kinuyo Ohno; Yasuhisa Matsui; Kanae Hara; Risa Gotoh; Mai Suzuki; Shinya Rai; Hirokazu Tanaka; Itaru Matsumura; Hiroshi Shima; Toshio Watanabe
    FEBS Letters 589 (19) 2754 - 2762 0014-5793 2015/09 [Refereed]
     
    © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. In mammals, the small Arf GTPase-activating protein (SMAP) subfamily of Arf GTPase-activating proteins consists of closely related members, SMAP1 and SMAP2. These factors reportedly exert distinct functions in membrane trafficking, as manifested by different phenotypes seen in single knockout mice. The present study investigated whether SMAP proteins interact genetically. We report for the first time that simultaneous loss of SMAP1 and SMAP2 promotes apoptosis in the distal region of E7.5 mouse embryos, likely resulting in embryonic lethality. Thus, at least one SMAP gene, either SMAP1 or SMAP2, is required for proper embryogenesis.
  • 症候性骨髄腫969症例における腎障害の後方視的解析(関西骨髄腫フォーラム)
    金子 仁臣; 八木 秀男; 小原 尚恵; 柴山 浩彦; 田中 宏和; 淵田 真一; 木田 亨; 小杉 智; 黒田 純也; 太田 健介; 新堂 真紀; 小林 正行; 上辻 由里; 中谷 綾; 足立 陽子; 河田 英里; 内山 人二; 魚嶋 伸彦; 浦瀬 文明; 高橋 隆幸; 高橋 良一; 飯田 正人; 松村 到; 日野 雅之; 金倉 譲; 島崎 千尋; 谷脇 雅史; 野村 昌作; 通堂 満; 高折 晃史
    臨床血液 (一社)日本血液学会-東京事務局 56 (9) 1800 - 1800 0485-1439 2015/09
  • Midori Yanagihara; Naoki Oiso; Hirokazu Tanaka; Tomohiko Narita; Eisuke Enoki; Masatomo Kimura; Hirokazu Nakamine; Itaru Matsumura; Akira Kawada
    Journal of Dermatology WILEY-BLACKWELL 42 (8) 844 - 845 0385-2407 2015/08 [Refereed]
  • 田中宏和; 松村到
    血液フロンティア 25 (7) 977 - 986 1344-6940 2015/06
  • 森田泰慶; 田中宏和; 松村到
    月刊血液内科 (有)科学評論社 70 (5) 612 - 616 2185-582X 2015/05
  • 田中宏和; 松村到
    がん分子標的治療 13 (1) 37 - 45 1347-6955 2015/04
  • 平瀬主税; 田中宏和; 松村到
    月刊血液内科 (有)科学評論社 70 (2) 140 - 148 2185-582X 2015/02
  • Hirokazu Tanaka; Chikara Hirase; Itaru Matsumura
    [Rinshō ketsueki] The Japanese journal of clinical hematology (一社)日本血液学会-東京事務局 56 (2) 139 - 149 0485-1439 2015/02 [Refereed]
     
    Tyrosine kinase inhibitors (TKIs) have dramatically improved the clinical outcomes of patients with chronic myeloid leukemia (CML) in the chronic phase. However, even if these patients achieve and maintain marked molecular responses such as a complete molecular response (BCR-ABL/ABL≤0.032% by international scale), discontinuation of TKI treatment results in early molecular relapse in most cases. Although several factors such as the Sokal score and the duration of TKI treatment have been identified as being related to treatment-free remission (TFR), identification of more definite factors or clinical conditions that would enable us to select patients who can maintain TFR is required. Relapse after TKI discontinuation is considered to be attributable to CML stem cells surviving even in patients who maintain marked molecular responses. A number of in vitro experiments have shown that TKI by itself cannot kill CML stem cells. Also, CML stem cells are resistant to TKI in a manner dependent on self-renewal factors (Hh, Wnt/β-catenin), cell cycle regulators (PML), metabotropic factors (FOXO3, Alox5), and adhesion molecules (CXCR4). In addition, surface markers specific for CML stem cells such as IL-1RAP and CD26 have been identified. New therapeutic strategies targeting these molecules in combination with TKI hold promise of achieving a more effective strategy for curing CML.
  • Tsutomu Kobayashi; Junya Kuroda; Shin-ichi Fuchida; Hitomi Kaneko; Hideo Yagi; Hirohiko Shibayama; Hirokazu Tanaka; Satoru Kosugi; Nobuhiko Uoshima; Masayuki Kobayashi; Yoko Adachi; Kensuke Ohta; Kazuyoshi Ishii; Hitoji Uchiyama; Mitsuhiro Matsuda; Eiji Nakatani; Mitsuru Tsudo; Chihiro Shimazaki; Akifumi Takaori-Kondo; Shosaku Nomura; Itaru Matsumura; Masafumi Taniwaki; Yuzuru Kanakura
    INTERNATIONAL JOURNAL OF HEMATOLOGY SPRINGER JAPAN KK 101 (1) 37 - 45 0925-5710 2015/01 [Refereed]
     
    We retrospectively investigated the prognostic factor of lenalidomide plus low-dose dexamethasone (Rd) in Japanese patients with refractory or relapsed multiple myeloma (RRMM) registered in the Kansai Myeloma Forum from January 2006 to December 2013. A total of 140 patients were analyzed. The median age was 66 years. The overall response rate was 68.6 %, including 33.1 % with a better than very good partial response. At 13.0 months median follow-up, the median overall survival (OS) and progression-free survival (PFS) were 34.2 and 17.0 months, respectively. In univariate analyses, patients with one or two prior therapies had significantly longer OS (41.2 vs. 21.5 months; P = 0.002) and PFS (29.0 vs. 13.0 months; P = 0.006) than patients treated with three or more prior therapies. Prior use of thalidomide was associated with significantly shorter PFS (19.0 vs. 16.0 months; P = 0.045). The prior use of bortezomib or high-dose therapy with stem cell transplantation, and the International Staging System had no impact on long-term outcome. Multivariate analysis showed that only the number of prior therapies was a significant predictor of both OS and PFS. Our findings suggest that greater benefit may occur when Rd therapy is used at the first or second relapse in RRMM.
  • Yasuyoshi Morita; Masakatsu Emoto; Kentaro Serizawa; Shinya Rai; Chikara Hirase; Yoshitaka Kanai; Yasuyo Ohyama; Toshihiko Shiga; Hirokazu Tanaka; Junichi Miyatake; Yoichi Tatsumi; Takashi Ashida; Masatomo Kimura; Masafumi Ito; Itaru Matsumura
    INTERNAL MEDICINE JAPAN SOC INTERNAL MEDICINE 54 (11) 1393 - 1396 0918-2918 2015 [Refereed]
     
    A 68-year-old man was referred to our hospital due to a high fever and pancytopenia. Neither tumors nor infectious lesions were detected. Hemophagocytosis was observed on the bone marrow (BM) smear, although without abnormal cells. Prednisolone therapy was ineffective for the patient's high fever. Later on, we obtained the results of a BM biopsy indicating the presence of infiltration of atypical Reed-Sternberg cells, leading to a diagnosis of HIV-negative primary bone marrow Hodgkin lymphoma (PBMHL). However, the patient died of multiple organ failure before receiving chemotherapy. As the clinical course of PBMHL is rapid, physicians must keep in mind its possibility in similar cases.
  • Shinya Rai; Hirokazu Tanaka; Mai Suzuki; Honami Ogoh; Yasuhiro Taniguchi; Yasuyoshi Morita; Takahiro Shimada; Akira Tanimura; Keiko Matsui; Takafumi Yokota; Kenji Oritani; Kenji Tanabe; Toshio Watanabe; Yuzuru Kanakura; Itaru Matsumura
    PLOS ONE PUBLIC LIBRARY SCIENCE 9 (10) e109441  1932-6203 2014/10 [Refereed]
     
    CALM is implicated in the formation of clathrin-coated vesicles, which mediate endocytosis and intracellular trafficking of growth factor receptors and nutrients. We previously found that CALM-deficient mice suffer from severe anemia due to the impaired clathrin-mediated endocytosis of transferrin receptor in immature erythroblast. However, CALM has been supposed to regulate the growth and survival of hematopoietic stem/progenitor cells. So, in this study, we focused on the function of CALM in these cells. We here show that the number of Linage(-)Sca-1(+)KIT(+) (LSK) cells decreased in the fetal liver of CALM(-/-) mice. Also, colony forming activity was impaired in CALM(-/-) LSK cells. In addition, SCF, FLT3, and TPO-dependent growth was severely impaired in CALM(-/-) LSK cells, while they can normally proliferate in response to IL-3 and IL-6. We also examined the intracellular trafficking of KIT using CALM(-/-) murine embryonic fibroblasts (MEFs) engineered to express KIT. At first, we confirmed that endocytosis of SCF-bound KIT was not impaired in CALM(-/-) MEFs by the internalization assay. However, SCF-induced KIT trafficking from early to late endosome was severely impaired in CALM(-/-) MEFs. As a result, although intracellular KIT disappeared 30 min after SCF stimulation in wild-type (WT) MEFs, it was retained in CALM(-/-) MEFs. Furthermore, SCF-induced phosphorylation of cytosolic KIT was enhanced and prolonged in CALM(-/-) MEFs compared with that in WT MEFs, leading to the excessive activation of Akt. Similar hyperactivation of Akt was observed in CALM(-/-) KIT+ cells. These results indicate that CALM is essential for the intracellular trafficking of KIT and its normal functions. Also, our data demonstrate that KIT located in the early endosome can activate downstream molecules as a signaling endosome. Because KIT activation is involved in the pathogenesis of some malignancies, the manipulation of CALM function would be an attractive therapeutic strategy.
  • 田中宏和; 松村到
    医学のあゆみ 医歯薬出版 250 (1) 5 - 9 0039-2359 2014/07
  • 田中宏和; 松村到
    月刊血液内科 (有)科学評論社 68 (5) 572 - 578 2185-582X 2014/05
  • Akira Tanimura; Hirohiko Shibayama; Yuri Hamanaka; Natsuko Fujita; Tomohiko Ishibashi; Takao Sudo; Takafumi Yokota; Sachiko Ezoe; Hirokazu Tanaka; Itaru Matsumura; Kenji Oritani; Yuzuru Kanakura
    EXPERIMENTAL HEMATOLOGY ELSEVIER SCIENCE INC 42 (5) 410 - 422 0301-472X 2014/05 [Refereed]
     
    Anamorsin (AM) is an antiapoptotic molecule that confers factor-independent survival on hematopoietic cells. AM-deficient (AM(-/-)) mice are embryonic lethal because of a defect in definitive hematopoiesis; however, the significance of AM in embryonic hematopoiesis remains unknown. This study characterized the hematopoietic defects in AM(-/-) fetal livers. The AM(-/-) fetal liver displayed significantly reduced numbers of c-Kit(+)Sca-1(+)Lin(-) (KSL) cells. An in vitro colony-forming unit assay showed that fetal liver cells isolated from AM(-/-) embryos gave rise to fewer colonies in all cell types. The reconstitution activity in AM(-/-) hematopoietic stem cells (HSCs) was markedly reduced in all lineages. Furthermore, the limiting dilution assay revealed that the number of fetal liver HSCs was reduced because of AM deficiency. Retrovirus-mediated AM expression rescued the defective hematopoietic colony-forming activities of AM(-/-) KSL cells. We also investigated the effects of AM deficiency on fetal liver stromal cells, which support hematopoiesis. Interestingly, primary stromal cell cultures from wild type fetal liver supported the growth of AM(-/-) KSL cells, but stromal cultures from AM(-/-) fetal liver provided little support of wild type KSL cell growth. These results demonstrated that AM was essential for both autonomous and extrinsic regulation of fetal liver hematopoiesis. This study provided new insight into the molecular regulation of hematopoiesis. (C) 2014 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.
  • Junya Kuroda; Yuji Shimura; Kensuke Ohta; Hirokazu Tanaka; Hirohiko Shibayama; Satoru Kosugi; Shinichi Fuchida; Masayuki Kobayashi; Hitomi Kaneko; Nobuhiko Uoshima; Kazuyoshi Ishii; Shosaku Nomura; Masafumi Taniwaki; Akifumi Takaori-Kondo; Chihiro Shimazaki; Mitsuru Tsudo; Masayuki Hino; Itaru Matsumura; Yuzuru Kanakura
    INTERNATIONAL JOURNAL OF HEMATOLOGY SPRINGER JAPAN KK 99 (4) 441 - 449 0925-5710 2014/04 [Refereed]
     
    We retrospectively investigated clinical outcomes and prognostic factors of 131 patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM) who received melphalan and prednisolone (MP) as first-line therapy from 2006 to 2013. Eighty-one patients received salvage therapies incorporating bortezomib, lenalidomide, and/or thalidomide. The overall response rate to MP was 54.2 %, including 9.2 % of better than very good partial response. With a median follow-up period of 30.2 months, median overall survival (OS) and median time to next treatment (TNT) were 54.4 and 19.0 months, respectively. Univariate analysis revealed that performance status and serum calcium level significantly associated with both OS and TNT, and multivariate analysis revealed that the higher serum calcium level had a significantly unfavorable impact on OS and TNT. Importantly, staging informed by the international staging system (ISS) was not predictive for OS or TNT in the analyzed cohort. Our study revealed that, in the context of first-line MP therapy for NDMM, the salvage therapy incorporating novel agents produced a survival period of > 30 months after the initiation of second-line therapy, suggesting that the predictive value of ISS for OS and TNT may be limited in the era of novel agents.
  • 平瀬主税; 田中宏和; 松村到
    月刊血液内科 (有)科学評論社 68 (3) 399 - 404 2185-582X 2014/03
  • 森田泰慶; 田中宏和; 松村到
    Medicina (株)医学書院 51 (3) 430 - 433 0025-7699 2014/03 
    ＜ポイント＞白血球増加症には,造血器腫瘍による場合と類白血病反応の場合がある.敗血症,粟粒結核などの重篤な感染症時には,末梢血中に種々の分化段階の未熟な顆粒球系細胞の出現を認める.がんの骨髄転移やG-CSF産生腫瘍では,CML様の白血球増多症が認められることがある.(著者抄録)
  • Nonoyama H; Tanigawa T; Tamaki T; Tanaka H; Yamamuro O; Ueda H
    Acta oto-laryngologica 134 (3) 221 - 226 0001-6489 2014/03 [Refereed]
  • 平瀬主税; 田中宏和; 松村到
    Annual Review 血液 2014 110 - 116 2014/01
  • Yusuke Satoh; Takafumi Yokota; Takao Sudo; Motonari Kondo; Anne Lai; Paul W Kincade; Taku Kouro; Ryuji Iida; Koichi Kokame; Toshiyuki Miyata; Yoko Habuchi; Keiko Matsui; Hirokazu Tanaka; Itaru Matsumura; Kenji Oritani; Terumi Kohwi-Shigematsu; Yuzuru Kanakura
    Immunity 38 (6) 1105 - 15 1074-7613 2013/06 [Refereed]
     
    How hematopoietic stem cells (HSCs) produce particular lineages is insufficiently understood. We searched for key factors that direct HSC to lymphopoiesis. Comparing gene expression profiles for HSCs and early lymphoid progenitors revealed that Satb1, a global chromatin regulator, was markedly induced with lymphoid lineage specification. HSCs from Satb1-deficient mice were defective in lymphopoietic activity in culture and failed to reconstitute T lymphopoiesis in wild-type recipients. Furthermore, Satb1 transduction of HSCs and embryonic stem cells robustly promoted their differentiation toward lymphocytes. Whereas genes that encode Ikaros, E2A, and Notch1 were unaffected, many genes involved in lineage decisions were regulated by Satb1. Satb1 expression was reduced in aged HSCs with compromised lymphopoietic potential, but forced Satb1 expression partly restored that potential. Thus, Satb1 governs the initiating process central to the replenishing of lymphoid lineages. Such activity in lymphoid cell generation may be of clinical importance and useful to overcome immunosenescence.
  • 平瀬主税; 田中宏和; 松村到
    日本臨床 67 - 72 0047-1852 2013/05
  • 田中宏和; 平瀬主税; 松村到
    日本臨床 80 - 82 0047-1852 2013/05
  • Takashi Ashida; Ami Kawano; Erika Yamada; Daisuke Ide; Chiemi Sugano; Yuko Kato; Yuko Tsubakimoto; Shiho Ito; Yoshiko Mine; Michiko Fujita; Yasushi Kanemitsu; Yoshiyuki Morishima; Yasuyoshi Morita; Hirokazu Tanaka; Takahiro Shimada; Kazunobu Kawanishi; Junichi Miyatake; Yoichi Tatsumi; Itaru Matsumura
    [Rinsho ketsueki] The Japanese journal of clinical hematology 54 (4) 365 - 9 0485-1439 2013/04 
    We retrospectively investigated the status of transfusional iron overload at Kinki University Hospital. One hundred and sixty three patients received more than 10 red blood cell (RBC) units per year in 2009 and 2010. Myelodysplastic syndrome (37.4%) and aplastic anemia (11.0%) accounted for about 50% of the underlying diseases. At the time of receiving a total of 20 RBC units, 90.8% and 66.2% of the 65 patients evaluated had more than 500 and 1,000 ng/ml of serum ferritin, respectively. The frequency of organ dysfunction associated with iron overload was 56.9% of all the patients assessed, 37.8% of patients with serum ferritin levels of 500∼999 ng/ml, and 67.4% of patients with serum ferritin levels >1,000 ng/ml. Although the Japanese guidelines propose 40 units of RBC transfusion and/or a serum ferritin level of 1,000 ng/ml as a good point to start iron chelation therapy, our results suggest that iron overload and consequent organ dysfunction may occur earlier than this. Therefore, it may be necessary to start iron chelation therapy earlier than that suggested by the Japanese guidelines.
  • 芦田 隆司; 川野 亜美; 山田 枝里佳; 井手 大輔; 菅野 知恵美; 加藤 祐子; 椿本 祐子; 伊藤 志保; 峯 佳子; 藤田 往子; 金光 靖; 森嶋 祥之; 森田 泰慶; 田中 宏和; 嶋田 高広; 川西 一信; 宮武 淳一; 辰巳 陽一; 松村 到
    臨床血液 (一社)日本血液学会-東京事務局 54 (4) 365 - 369 0485-1439 2013/04 
    今回,単一施設における輸血後鉄過剰症の実態を検討した。2009年と2010年の2年間に年間10単位以上の輸血を受けていた血液疾患患者は合計163例で,およそ半数が骨髄異形成症候群(61例)と再生不良性貧血(18例)であった。赤血球輸血が20単位施行された時点で血清フェリチン値が測定されていた65症例中血清フェリチン値が500ng/ml以上,1,000ng/ml以上であった症例の比率はそれぞれ90.8%,66.2%であった。鉄過剰症に関連すると推測される臓器障害の比率は,全体で56.9%,血清フェリチンが500〜999ng/mlでは43.8%,1,000ng/ml以上では67.4%であった。今回の解析により,「輸血後鉄過剰症の全国実態調査」の結果より早期に輸血後鉄過剰症が起こり,臓器障害も出現することが明らかになった。したがって,赤血球輸血40単位,血清フェリチン値1,000ng/mlを除鉄療法の開始基準とするわが国のガイドラインより早期に除鉄療法を開始する必要がある可能性が示唆された。(著者抄録)
  • Yasuyoshi Morita; Jun-Ichi Nishimura; Takahiro Shimada; Hirokazu Tanaka; Kentaro Serizawa; Yasuhiro Taniguchi; Mitsuhiro Tsuritani; Yuzuru Kanakura; Itaru Matsumura
    International Journal of Hematology 97 (4) 491 - 497 0925-5710 2013/04 [Refereed]
     
    Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired stem cell disorder characterized by intravascular hemolysis and thrombosis. The most serious complication is thrombosis, the risk of which is augmented by the hyper-coagulable state that occurs during pregnancy despite this risk, however, young female PNH patients often desire to have a baby. We recently experienced two successful deliveries in PNH patients, who were treated with anticoagulant therapy during their pregnancies. Meanwhile, given the potential benefit of eculizumab (Soliris), a humanized monoclonal antibody against C5, in reducing thrombosis and hemolysis, it represents a promising therapeutic option for the treatment of pregnant PNH patients in combination with, or in replacement of, anticoagulant therapy. © The Japanese Society of Hematology 2013.
  • 田中宏和; 松村到
    アニムス アニムス 75 (2) 11 - 15 1342-0119 2013/04
  • Shinya Rai; Mitsuhiro Matsuda; Nozomi Yamairi; Go Eguchi; Takayuki Iwanaga; Yasuyoshi Morita; Hirokazu Tanaka; Yoichi Tatsumi; Takashi Ashida; Itaru Matsumura
    Internal Medicine 52 (2) 273 - 276 0918-2918 2013 [Refereed]
     
    A 32-year-old woman was referred to our hospital due to systemic lymphadenopathy. The patient's peripheral blood showed expansion of CD5+CD20+CD38+CD23- mature lymphocytes. However, the axillary lymph nodes were infiltrated by both CD23+ large lymphocytes and CD23- small lymphocytes. Because the pattern of the rearranged immunoglobulin heavy chain gene was different between the peripheral blood and lymph node samples in a Southern blot analysis, the patient was diagnosed with Richter syndrome, in which diffuse large B-cell lymphoma develops from a clone distinct from B-cell chronic lymphocytic leukemia. After undergoing rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) therapy, the patient was successfully treated with allogeneic hematopoietic transplantation, and no relapse was observed for three years. © 2013 The Japanese Society of Internal Medicine.
  • Morita Y; Tanaka H; Matsumura I
    Nihon rinsho. Japanese journal of clinical medicine 70 Suppl 8 508 - 512 0047-1852 2012/11 [Refereed]
  • 【分子標的薬-がんから他疾患までの治癒をめざして-】 臨床研究 腫瘍性疾患の分子標的薬 骨髄異形成症候群
    森田 泰慶; 田中 宏和; 松村 到
    日本臨床 (株)日本臨床社 70 (増刊8 分子標的薬) 508 - 512 0047-1852 2012/11
  • 骨髄異形成症候群
    森田 泰慶; 田中 宏和; 松村 到
    日本臨牀 日本臨牀 70 (8) 508 - 512 2012/11
  • 【急性骨髄性白血病-分子異常と予後-】 正常核型AMLの遺伝子変異
    田中 宏和; 松村 到
    最新医学 (株)最新医学社 67 (10) 2406 - 2412 0370-8241 2012/10 
    急性骨髄性白血病(AML)の40〜50%は正常核型を有する.これまでAMLは,細胞増殖・生存にかかわるクラスI変異と細胞分化にかかわるクラスII変異が同時に起こって発症すると考えられてきた.しかし近年,エピジェネティクスにかかわる分子の遺伝子変異が多数明らかにされ,クラスIII変異と呼ばれるようになった.これらの遺伝子異常によって正常核型AMLの予後を層別化し,至適な治療法を確立することが今後の課題である.(著者抄録)
  • 正常核型AMLの遺伝子変異
    田中 宏和; 松村 到
    最新医学 最新医学社 67 (10) 24 - 30 2012/10
  • イマチニブ抵抗性・不耐容の慢性期CMLに対する治療方針
    田中 宏和; 松村 到
    EBM血液疾患の治療 2013-2014 中外医学社 2012/10
  • クロマチンおよびDNA修飾を標的とする分子的治療薬の開発：総論
    田中 宏和; 松村 到
    造血器腫瘍とエピジェネティクス 医薬ジャーナル社 160 - 167 2012/10
  • CMLの最新治療
    平瀨 主税; 田中 宏和; 松村 到
    Current Therapy Current Therapy 30 (10) 2012/10
  • Takao Sudo; Takafumi Yokota; Kenji Oritani; Yusuke Satoh; Tatsuki Sugiyama; Tatsuro Ishida; Hirohiko Shibayama; Sachiko Ezoe; Natsuko Fujita; Hirokazu Tanaka; Tetsuo Maeda; Takashi Nagasawa; Yuzuru Kanakura
    Journal of immunology (Baltimore, Md. : 1950) 189 (1) 200 - 10 2012/07 [Refereed]
     
    Whereas most hematopoietic stem cells (HSC) are quiescent in homeostasis, they actively proliferate in response to bone marrow (BM) injury. Signals from the BM microenvironment are thought to promote entry of HSC into the cell cycle. However, it has been cumbersome to assess cycle status of viable HSC and thus explore unique features associated with division. In this study, we show that expression of endothelial cell-selective adhesion molecule (ESAM) can be a powerful indicator of HSC activation. ESAM levels clearly mirrored the shift of HSC between quiescence and activation, and it was prominent in comparison with other HSC-related Ags. ESAM(hi) HSC were actively dividing, but had surprisingly high long-term reconstituting capacity. Immunohistochemical analyses showed that most ESAM(hi) HSC were located near vascular endothelium in the BM after 5-fluorouracil treatment. To determine the importance of ESAM in the process of BM recovery, ESAM knockout mice were treated with 5-fluorouracil and their hematopoietic reconstruction was examined. The ESAM deficiency caused severe and prolonged BM suppression, suggesting that ESAM is functionally indispensable for HSC to re-establish homeostatic hematopoiesis. With respect to intracellular regulators, NF-κB and topoisomerase II levels correlated with the ESAM upregulation. Thus, our data demonstrate that the intensity of ESAM expression is useful to trace activated HSC and to understand molecular events involved in stem cell states.
  • 田中 宏和; 松村 到
    血液内科 科学評論社 64 (6) 726 - 731 2185-582X 2012/06
  • Usuki K; Tojo A; Maeda Y; Kobayashi Y; Matsuda A; Ohyashiki K; Nakaseko C; Kawaguchi T; Tanaka H; Miyamura K; Miyazaki Y; Okamoto S; Oritani K; Okada M; Usui N; Nagai T; Amagasaki T; Wanajo A; Naoe T
    International journal of hematology 95 (4) 409 - 419 0925-5710 2012/04 [Refereed]
  • Satoh Y; Matsumura I; Tanaka H; Harada H; Harada Y; Matsui K; Shibata M; Mizuki M; Kanakura Y
    Leukemia 26 (2) 303 - 311 0887-6924 2012/02 [Refereed]
  • 【血液病ガイドラインupdate〜造血器腫瘍〜】 慢性骨髄性白血病
    田中 宏和; 松村 到
    血液フロンティア (株)医薬ジャーナル社 22 (3) 355 - 363 1344-6940 2012/02 
    慢性期の慢性骨髄性白血病(CML-CP)の治療成績は、チロシンキナーゼ阻害薬(TKI)が登場して画期的に改善した。イマチニブ投与時の治療効果判定およびその後の治療選択については、エビデンスが蓄積されてきた。第二世代TKIはイマチニブ抵抗性・不耐容例のみでなく、初発CML-CPに対してもイマチニブより高い治療効果を示すが、長期予後を含めたエビデンスの確立が今後の課題である。一方、移行期、急性転化期のCMLに対してはTKI単独では十分でなく、化学療法、同種造血幹細胞移植が必要とされる。CML治療においてはEuropean Leukemia Net(ELN)の推奨およびNCCNのガイドラインが一般に用いられている。(著者抄録)
  • Keiko Matsui; Sachiko Ezoe; Kenji Oritani; Masaru Shibata; Masahiro Tokunaga; Natsuko Fujita; Akira Tanimura; Takao Sudo; Hirokazu Tanaka; Michael W. McBurney; Itaru Matsumura; Yuzuru Kanakura
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS ACADEMIC PRESS INC ELSEVIER SCIENCE 418 (4) 811 - 817 0006-291X 2012/02 
    Sir2 has been shown to be essential for transcriptional silencing and longevity provided by calorie restriction in Saccharomyces cerevisiae and Caenorhabditis elegans. In this study, we investigated the role for its mammalian homologue, SIRT1, in hematopoietic cells. SIRT1 inhibitor, nicotinamide (NA), promoted and its activator, resveratrol, inhibited the differentiation of murine bone marrow c-Kit(high)Sca-1(+)Lineage(-) (KSL) cells during the culture system ex vivo. To further clarify the roles of SIRT1 in hematopoietic cells, we isolated KSL cells from fetal liver of SIRT1 knockout (KO) mice and cultured them for 5 days, because SIRT1 KO mice die shortly after the delivery. In agreement with the results from the experiments using NA and resveratrol, KSL cells isolated from SIRT1 KO mice more apparently differentiated and lost the KSL phenotype than those from wild-type (WT) mice. Furthermore, in each of colony assay, replating assay, or serial transplantation assay, SIRT1 KO KSL cells lost earlier the characteristics of stem cells than WT KSL cells. In addition, we found that SIRT1 maintains prematurity of hematopoietic cells through ROS elimination, FOXO activation, and p53 inhibition. These results suggest that SIRT1 suppresses differentiation of hematopoietic stem/progenitor cells and contributes to the maintenance of stem cell pool. (C) 2012 Elsevier Inc. All rights reserved.
  • Mai Suzuki; Hirokazu Tanaka; Akira Tanimura; Kenji Tanabe; Natsuko Oe; Shinya Rai; Syunsuke Kon; Manabu Fukumoto; Kohji Takei; Takaya Abe; Itaru Matsumura; Yuzuru Kanakura; Toshio Watanabe
    PLOS ONE PUBLIC LIBRARY SCIENCE 7 (2) 1 - 12 1932-6203 2012/02 
    Phosphatidylinositol binding clathrin assembly protein (PICALM), also known as clathrin assembly lymphoid myeloid leukemia protein (CALM), was originally isolated as part of the fusion gene CALM/AF10, which results from the chromosomal translocation t(10;11)(p13;q14). CALM is sufficient to drive clathrin assembly in vitro on lipid monolayers and regulates clathrin-coated budding and the size and shape of the vesicles at the plasma membrane. However, the physiological role of CALM has yet to be elucidated. Here, the role of CALM in vivo was investigated using CALM-deficient mice. CALM-deficient mice exhibited retarded growth in utero and were dwarfed throughout their shortened life-spans. Moreover, CALM-deficient mice suffered from severe anemia, and the maturation and iron content in erythroid precursors were severely impaired. CALM-deficient erythroid cells and embryonic fibroblasts exhibited impaired clathrin-mediated endocytosis of transferrin. These results indicate that CALM is required for erythroid maturation and transferrin internalization in mice.
  • 慢性骨髄性白血病
    松村 到; 田中 宏和
    血液フロンティア 医薬ジャーナル社 22 (3) 33 - 41 2012/02
  • ニロチニブの最適な用量
    松村 到; 田中 宏和
    腫瘍内科 科学評論社 9 (2) 186 - 190 2012/02
  • Kazunobu Kawanishi; Yasuyo Ohyama; Yoshitake Kanai; Tikara Hirase; Hirokazu Tanaka; Junichi Miyatake; Youichi Tatsumi; Takashi Ashida; Hirokazu Nakamine; Itaru Matsumura
    INTERNAL MEDICINE JAPAN SOC INTERNAL MEDICINE 51 (15) 2015 - 2020 0918-2918 2012 [Refereed]
     
    Here we report the first case of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), who initially presented with peripheral neuropathy. Nerve conduction, cerebral spinal fluid studies and his clinical course were compatible with sub-acute demyelinating polyradiculoneuropathy. In addition, left cervical lymph node swelling was observed on admission. Diagnosis of PTCL-NOS was made by the histological, immuno-histochemical, and Southern blot analyses on the biopsy specimen from the enlarged lymph node. Combination chemotherapy composed of cyclophosphamide, vincristine, doxorubicin and prednisolone (CHOP) was effective for polyneuropathy as well as for lymphoma. Several antibodies relating to paraneoplastic syndrome such as Ma1, Ma2, Amphiphysin, CV2, Ri, Yo and Hu were all negative. Because sural nerve biopsy performed prior to CHOP therapy revealed no infiltration of lymphoma cells, immune dysfunction mediated by some cytokine or unidentified autoantibody related to PTCL-NOS was thought to be involved in the polyradiculoneuropathy.
  • Yusuke Satoh; Takafumi Yokota; Motonari Kondo; Paul W. Kincade; Taku Kouro; Ryuji Iida; Koichi Kokame; Toshiyuki Miyata; Takao Sudo; Hirokazu Tanaka; Itaru Matsumura; Kenji Oritani; Terumi Kohwi-Shigematsu; Yuzuru Kanakura
    BLOOD AMER SOC HEMATOLOGY 118 (21) 179 - 179 0006-4971 2011/11 [Refereed]
  • Yuri Saito; Hirohiko Shibayama; Hirokazu Tanaka; Akira Tanimura; Itaru Matsumura; Yuzuru Kanakura
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS ACADEMIC PRESS INC ELSEVIER SCIENCE 408 (2) 329 - 333 0006-291X 2011/05 [Refereed]
     
    Anamorsin (AM) (also called CIAPIN-1) is a cell-death-defying factor. AM deficient mice die during late gestation; AM deficient embryos are anemic and very small compared to wild type (WT) embryos. It is thought that AM plays crucial roles in hematopoiesis and embryogenesis. To clarify the mechanisms of AM functions, we performed the yeast-two-hybrid assay to identify AM-interacting molecules; we found that PICOT (PKC theta interacting cousin of thioredoxin) preferentially bound to AM. We also showed that the N-terminal regions of both AM and PICOT were essential for their bindings and the inhibition of interaction of both molecules might lead to the cell growth retardation. Both PICOT and the yeast homolog of AM are known to be iron-sulfur proteins. The phenotype of PICOT deficient mice is very similar to that of anamorsin deficient mice; both mice are embryonic lethal. These data suggest that AM and PICOT might play cooperatively essential roles in embryogenesis as iron-sulfur cluster proteins. (C) 2011 Elsevier Inc. All rights reserved.
  • Jiro Fujita; Masao Mizuki; Masayasu Otsuka; Sachiko Ezoe; Hirokazu Tanaka; Yusuke Satoh; Kentaro Fukushima; Masahiro Tokunaga; Itaru Matsumura; Yuzuru Kanakura
    IMMUNOLOGY LETTERS ELSEVIER SCIENCE BV 136 (1) 61 - 73 0165-2478 2011/04 [Refereed]
     
    Dendritic cells (DCs) play important roles in tumor immunology. Leukemic cells in patients with myeloid neoplasms can differentiate into DCs in vivo (referred to as in vivo leukemic DCs), which are postulated to affect anti-leukemia immune responses. We established a reproducible culture system of in vitro FLT3 ligand-mediated DC (FL-DC) differentiation from murine lineage(-) Sca-1(+) c-Kit(high) cells (LSKs), which made it possible to analyse the effects of target genes on steady-state DC differentiation from hematopoietic stem/progenitor cells. Using this system, we analysed the effects of various myeloid neoplasm-related gene abnormalities, termed class I and class II mutations, on FL-DC differentiation from LSKs. All class II mutations uniformly impaired FL-DC differentiation maintaining a plasmacytoid DC (pDC)/conventional DC (cDC) ratio comparable to the control cells. In contrast, class I mutations differentially affected FL-DC differentiation from LSKs. FLT3-ITD and a constitutively active form of Ras (CA-N-Ras) yielded more FL-DCs than the control, whereas the other class I mutations tested yielded less FL-DCs. Both FLT3-ITD and FLT3-tyrosine kinase domain (TKD) mutation showed a comparable pDC/cDC ratio as the control. CA-N-Ras, c-Kit-TKD, TEL/PDGFR beta, and FIP1L1 /PDGFR alpha showed a severe decrease in the pDC/cDC ratio. CA-STAT5 and CA-MEK1 severely inhibited pDC differentiation. FLT3-ITD, CA-N-Ras, and TEL/PDGFR beta aberrantly induced programmed death ligand-1 (PD-L1)-expressing DCs. In conclusion, we have established a simple, efficient, and reproducible in vitro FL-DC differentiation system from LSKs. This system could uncover novel findings on how myeloid neoplasm-related gene abnormalities differentially affect FL-DC differentiation from murine hematopoietic stem/progenitor cells in a gene-specific manner. (C) 2011 Elsevier B.V. All rights reserved.
  • Yuri Saito; Hirohiko Shibayama; Hirokazu Tanaka; Akira Tanimura; Yuzuru Kanakura
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS ACADEMIC PRESS INC ELSEVIER SCIENCE 405 (2) 303 - 307 0006-291X 2011/02 [Refereed]
     
    Anamorsin (AM) plays crucial roles in hematopoiesis and embryogenesis. AM deficient (AM KO) mice die during late gestation; AM KO embryos are anemic and very small compared to wild type (WT) embryos. To determine which signaling pathways AM utilizes for these functions, we used murine embryonic fibroblast (MEF) cells generated from E-14.5 AM KO or WF embryos. Proliferation of AM KO MEF cells was markedly retarded, and PKC theta, PKC delta, and p38MAPK were more highly phosphorylated in AM KO MEF cells. Expression of cyclinD1, the target molecule of p38MAPK, was down-regulated in AM KO MEF cells. p38MAPK inhibitor as well as PKC inhibitor restored expression of cyclinD1 and cell growth in AM KO MEF cells. These data suggest that PKC theta, PKC delta, and p38MAPK activation lead to cell cycle retardation in AM KO MEF cells, and that AM may negatively regulate novel PKCs and p38MAPK in MEF cells. (C) 2011 Elsevier Inc. All rights reserved.
  • Jiro Fujita; Masao Mizuki; Masayasu Otsuka; Sachiko Ezoe; Hirokazu Tanaka; Yusuke Satoh; Kentaro Fukushima; Masahiro Tokunaga; Itaru Matsumura; Yuzuru Kanakura
    BLOOD AMER SOC HEMATOLOGY 116 (21) 1592 - 1592 0006-4971 2010/11 [Refereed]
  • Masahiro Tokunaga; Sachiko Ezoe; Hirokazu Tanaka; Yusuke Satoh; Kentaro Fukushima; Keiko Matsui; Masaru Shibata; Akira Tanimura; Kenji Oritani; Itaru Matsumura; Yuzuru Kanakura
    JOURNAL OF BIOLOGICAL CHEMISTRY AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC 285 (41) 31774 - 31782 0021-9258 2010/10 [Refereed]
     
    BCR-ABL is a causative tyrosine kinase (TK) of chronic myelogenous leukemia (CML). In CML patients, although myeloid cells are remarkably proliferating, erythroid cells are rather decreased and anemia is commonly observed. This phenotype is quite different from that observed in polycythemia vera (PV) caused by JAK2 V617F, whereas both oncogenic TKs activate common downstream molecules at the level of hematopoietic stem cells (HSCs). To clarify this mechanism, we investigated the effects of BCR-ABL and JAK2 V617F on erythropoiesis. Enforced expression of BCR-ABL but not of JAK2 V617F in murine LSK (Lineage(-)Sca-1(hi)CD117(hi)) cells inhibited the development of erythroid cells. Among several signaling molecules downstream of BCR-ABL, an active mutant of N-Ras (N-RasE12) but not of STAT5 or phosphatidylinositol 3-kinase (PI3-K) inhibited erythropoiesis, while N-RasE12 enhanced the development of myeloid cells. BCR-ABL activated Ras signal more intensely than JAK2 V617F, and inhibition of Ras by manumycin A, a farnesyltransferase inhibitor, ameliorated erythroid colony formation of CML cells. As for the mechanisms of Ras-induced suppression of erythropoiesis, we found that GATA-1, an erythroid-specific transcription factor, blocked Ras-mediated mitogenic signaling at the level of MEK through the direct interaction. Furthermore, enforced expression of N-RasE12 in LSK cells derived from p53-, p16(INK4a)/p19(ARF)-, and p21(CIP1/WAF1)-null/wild-type mice revealed that suppressed erythroid cell growth by N-RasE12 was restored only by p21(CIP1/WAF1) deficiency, indicating that a cyclin-dependent kinase (CDK) inhibitor, p21(CIP1/WAF1), plays crucial roles in Ras-induced suppression of erythropoiesis. These data would, at least partly, explain why respective oncogenic TKs cause different disease phenotypes.
  • 抗細胞死分子アナモルシンは、p38MAPKを不活化し細胞増殖をもたらす(A cell-death-defying factor, anamorsin, yields cell growth through inactivation of p38 MAPK)
    斉藤 有理; 柴山 浩彦; 田中 宏和; 谷村 朗; 松村 到; 金倉 譲
    日本癌学会総会記事 日本癌学会 69回 168 - 168 0546-0476 2010/08
  • 田中宏和; 金倉譲; 松村到
    新たな移植細胞療法に向けた造血幹細胞のex vivo増幅技術の開発と応用 平成21年度 総括・分担研究報告書 43 - 49 2010
  • Yusuke Satoh; Itaru Matsumura; Hirokazu Tanaka; Hironori Harada; Yuka Harada; Yuzuru Kanakura
    BLOOD AMER SOC HEMATOLOGY 114 (22) 80 - 81 0006-4971 2009/11 [Refereed]
  • 田中宏和; 松村到; 金倉譲
    Biotherapy (Tokyo) (株)癌と化学療法社 23 (5) 364 - 370 0914-2223 2009/09 
    がん組織は多様な細胞集団から構成されるが、白血病など多くの腫瘍において腫瘍のなかの一部の細胞集団のみがNOD/SCIDマウスに移植した際に、元の腫瘍に類似した腫瘍を作ることが示されてきた。この概念は骨髄性白血病においても最も理解されており、これらの細胞が白血病幹細胞として定義されている。白血病幹細胞は正常造血幹細胞と同様に未分化な表面形質を示し、自己複製能と分化能を有することで白血病幹細胞集団を維持しつつ、白血病組織を構成する多様な分化段階にあるすべての白血病細胞を生みだす。正常造血幹細胞と同様に、白血病幹細胞も「白血病ニッチ」と呼ばれる微小環境を必要とし、その場で自己複製、生存に必要なNotch、Wnt/β-catenin、Sonic hedgehogなどからのシグナルを伝達される。白血病幹細胞の起源としては、もともと自己複製能を有していた正常造血幹細胞に遺伝子異常が起こった可能性と、自己複製能を有さない前駆細胞レベルに自己複製能を寄与する遺伝子異常が起こった可能性がある。白血病組織を形成する白血病幹細胞以外の白血病細胞は限られた分裂能しか有さず、いずれアポトーシスを起こしていくので、白血病を治癒させるには白血病幹細胞のみを死滅させれば十分である。しかし、白血病幹細胞は正常造血幹細胞と同様に細胞周期の静止期にあることから、通常の白血病治療には抵抗性であると想定されている。現在、自己複製能を阻害する薬剤などが開発中であるが、これらの薬剤は正常造血道細胞を阻害することは免れない。したがって、白血病幹細胞を選択的に死滅させる薬剤の開発が必要である。そのためには、抗体療法のための白血病幹細胞特異的抗原の同定や、直接の治療標的となる白血病幹細胞においてのみ活性化している分子、白血病幹細胞の自己複製や生存にのみかかわっている分子の同定が有用である。(著者抄録)
  • Kentaro Fukushima; Itaru Matsumura; Sachiko Ezoe; Masahiro Tokunaga; Masato Yasumi; Yusuke Satoh; Hirohiko Shibayama; Hirokazu Tanaka; Atsushi Iwama; Yuzuru Kanakura
    The Journal of biological chemistry 284 (12) 7719 - 32 0021-9258 2009/03 [Refereed]
     
    Although leukemogenic tyrosine kinases (LTKs) activate a common set of downstream molecules, the phenotypes of leukemia caused by LTKs are rather distinct. Here we report the molecular mechanism underlying the development of hypereosinophilic syndrome/chronic eosinophilic leukemia by FIP1L1-PDGFRalpha. When introduced into c-Kit(high)Sca-1(+)Lineage(-) cells, FIP1L1-PDGFRalpha conferred cytokine-independent growth on these cells and enhanced their self-renewal, whereas it did not immortalize common myeloid progenitors in in vitro replating assays and transplantation assays. Importantly, FIP1L1-PDGFRalpha but not TEL-PDGFRbeta enhanced the development of Gr-1(+)IL-5Ralpha(+) eosinophil progenitors from c-Kit(high)Sca-1(+)Lineage(-) cells. FIP1L1-PDGFRalpha also promoted eosinophil development from common myeloid progenitors. Furthermore, when expressed in megakaryocyte/erythrocyte progenitors and common lymphoid progenitors, FIP1L1-PDGFRalpha not only inhibited differentiation toward erythroid cells, megakaryocytes, and B-lymphocytes but aberrantly developed eosinophil progenitors from megakaryocyte/erythrocyte progenitors and common lymphoid progenitors. As for the mechanism of FIP1L1-PDGFRalpha-induced eosinophil development, FIP1L1-PDGFRalpha was found to more intensely activate MEK1/2 and p38(MAPK) than TEL-PDGFRbeta. In addition, a MEK1/2 inhibitor and a p38(MAPK) inhibitor suppressed FIP1L1-PDGFRalpha-promoted eosinophil development. Also, reverse transcription-PCR analysis revealed that FIP1L1-PDGFRalpha augmented the expression of C/EBPalpha, GATA-1, and GATA-2, whereas it hardly affected PU.1 expression. In addition, short hairpin RNAs against C/EBPalpha and GATA-2 and GATA-3KRR, which can act as a dominant-negative form over all GATA members, inhibited FIP1L1-PDGFRalpha-induced eosinophil development. Furthermore, FIP1L1-PDGFRalpha and its downstream Ras inhibited PU.1 activity in luciferase assays. Together, these results indicate that FIP1L1-PDGFRalpha enhances eosinophil development by modifying the expression and activity of lineage-specific transcription factors through Ras/MEK and p38(MAPK) cascades.
  • 田中宏和; 金倉譲; 松村到
    新たな移植細胞療法に向けた造血幹細胞のex vivo増幅技術の開発と応用 平成20年度 総括・分担研究報告書 65 - 71 2009
  • Hirokazu Tanaka; Itaru Matsumura; Yusuke Satoh; Sachiko Ezoe; Tatsutoshi Nakahata; Yuzuru Kanakura
    BLOOD AMER SOC HEMATOLOGY 112 (11) 847 - 847 0006-4971 2008/11 [Refereed]
  • Yusuke Satoh; Itaru Matsumura; Hirokazu Tanaka; Sachiko Ezoe; Kentaro Fukushima; Masahiro Tokunaga; Masato Yasumi; Hirohiko Shibayama; Masao Mizuki; Takumi Era; Tsukasa Okuda; Yuzuru Kanakura
    JOURNAL OF BIOLOGICAL CHEMISTRY AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC 283 (44) 30045 - 30056 0021-9258 2008/10 [Refereed]
     
    In this study, we analyzed the roles for AML1/RUNX1 in the regulation of the c-mpl promoter. Wild-type AML1 activated the c-mpl promoter through the proximal AML-binding site in luciferase assays using 293T and HeLa cells. In accord with this result, electrophoretic mobility shift assay and chromatin immunoprecipitation assays demonstrated that AML1 bound to this site. Next, we analyzed the function of AML1 using a mutant of AML1 lacking the C terminus (AML1dC), which was originally found in a patient with myelodysplastic syndromes. AML1dC dominant-negatively suppressed transcriptional activity of wild-type AML1. However, unexpectedly, AML1dC-transduced murine c-Kit(+)Sca1(+)Lineage(-) cells expressed c-mpl mRNA and c-Mpl protein more abundantly than mock-transduced cells, which led to the enhanced thrombopoietin-mediated proliferation. Moreover, when AML1dC was induced to express during the development of hematopoietic cells from embryonic stem (ES) cells, AML1dC augmented the c-Mpl expression on hematopoietic stem/progenitor cells. Furthermore, we found that early hematopoietic cells that derived from AML1(-/-) ES cells expressed c-Mpl more intensely than those that developed from wild-type ES cells. In contrast, AML1dC hardly affected c-Mpl expression and maturation of megakaryocytes. As for the mechanism of the different roles of AML1 in the regulation of the c-mpl promoter, we found that AML1 forms a complex with a transcription repressor mSin3A on the c-mpl promoter in hematopoietic stem/progenitor cells, although it forms a complex with a transcription activator p300 on the same promoter in megakaryocytic cells. Together, these data indicate that AML1 can regulate the c-mpl promoter both positively and negatively by changing the binding partner according to cell types.
  • Yanagihara K; Takigahira M; Tanaka H; Arao T; Aoyagi Y; Oda T; Ochiai A; Nishio K
    Cancer Sci 99 (9) 1859 - 64 1347-9032 2008/09 [Refereed]
  • Kamitsuji, Y; Kuroda, J; Kimura, S; Toyokuni, S; Watanabe, K; Ashihara, E; Tanaka, H; Watanabe, M; Matsubara, H; Mizushima, Y; Hiraumi, Y; Kawata, E; Yoshikawa, T; Maekawa, T; Nakahata, T; Adachi, S
    Cell Death Diff, 15(11):1712-1722. 2008 [Refereed]
  • 田中宏和; 金倉譲; 松村到
    サイトカインによる増幅培養臍帯血による臍帯血移植の臨床試験 平成19年度 総括・分担研究報告書 59 - 68 2008
  • Kuroda J; Kimura S; Andreeff M; Ashihara E; Kamitsuji Y; Yokota A; Kawata E; Takeuchi M; Tanaka R; Murotani Y; Matsumoto Y; Tanaka H; Strasser A; Taniwaki M; Maekawa T
    British journal of haematology 140 (2) 181 - 190 0007-1048 2008/01 [Refereed]
  • Kentaro Fukushima; Itaru Matsumura; Sachiko Ezoe; Hirohiko Shibayama; Michiko Ichii; Takafumi Yokota; Hirokazu Tanaka; Yuzuru Kanakura
    BLOOD AMER SOC HEMATOLOGY 110 (11) 300A - 300A 0006-4971 2007/11 [Refereed]
  • 腫瘍性チロシンキナーゼによる病型決定機構 FIP1L1/PDGFRαによる好酸球系細胞への選択的誘導
    福島 健太郎; 松村 到; 江副 幸子; 佐藤 友亮; 水木 満佐央; 田中 宏和; 織谷 健司; 金倉 譲
    臨床血液 (一社)日本血液学会-東京事務局 48 (9) 917 - 917 0485-1439 2007/09
  • 田中宏和; 金倉譲; 松村到
    サイトカインによる増幅培養臍帯血による臍帯血移植の臨床試験 平成18年度 総括・分担研究報告書 71 - 78 2007
  • Hirokazu Tanaka; Itaru Matsumura; Kazuki Nakao; Takumi Era; Yuzuru Kanakura
    BLOOD AMER SOC HEMATOLOGY 108 (11) 339A - 339A 0006-4971 2006/11 [Refereed]
  • Hirokazu Tanaka; Itaru Matsumura; Kiminari Itoh; Asako Hatsuyama; Masayuki Shikamura; Yusuke Satoh; Toshio Heike; Tatsutoshi Nakahata; Yuzuru Kanakurab
    STEM CELLS ALPHAMED PRESS 24 (11) 2592 - 2602 1066-5099 2006/11 [Refereed]
     
    HOX transcription factors play important roles in the self-renewal of hematopoietic cells. HOX proteins interact with the non-HOX homeobox protein PBX1 to regulate, both positively and negatively, the expression of target genes. In this study, we synthesized a decoy peptide containing the YPWM motif from HOX proteins ( decoy HOX [decHOX]), which was predicted to act as a HOX mimetic, and analyzed its effects on self-renewal of human cord blood CD34(+) cells. We were able to deliver decHOX into approximately 70% of CD34(+) cells. By examining the expression of HOX target genes c-myc and p21(waf1/cip1), we confirmed that decHOX enhanced HOX functions. After 7 days of culture in serum-free medium containing a cytokine cocktail, cultures treated with decHOX had approximately twofold-increased numbers of CD34(+) cells and primitive multipotent progenitor cells compared with control cells. Furthermore, decHOX-treated cells reconstituted hematopoiesis in nonobese diabetic/severe combined immunodeficiency mice more rapidly and more effectively ( more than twofold greater efficiency, as determined by a limiting dilution method) than control cells. decHOX-treated cells were also able to repopulate secondary recipients. Together, these results indicate that in combination with growth factors and/or other approaches, decHOX might be a useful new tool for the ex vivo expansion of hematopoietic stem/progenitor cells.
  • 田中宏和; 金倉譲; 松村到
    サイトカインによる増幅培養臍帯血移植の臨床試験 平成17年度 総括・分担研究報告書 76 - 83 2006
  • Yanagihara K; Takigahira M; Tanaka H; Komatsu T; Fukumoto H; Koizumi F; Nishio K; Ochiya T; Ino Y; Hirohashi S
    Cancer Sci 96 (6) 323 - 332 1347-9032 2005/06 [Refereed]
  • E Ishiko; Matsumura, I; S Ezoe; K Gale; J Ishiko; Y Satoh; H Tanaka; H Shibayama; M Mizuki; T Era; T Enver; Y Kanakura
    JOURNAL OF BIOLOGICAL CHEMISTRY AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC 280 (6) 4929 - 4939 0021-9258 2005/02 
    The effects of Notch signals on the erythroid/ imegakaryocytic differentiation of hematopoietic cells were examined. Activation of Notch signals by the intracellular Notch1 or an estradiol-inducible form of Notch1/ER suppressed the expression of the erythroid marker glycophorin A in an erythroid/megakaryocytic cell line K562. Although Mock-transfected K562 cells underwent megakaryocytic differentiation in response to '12-O-tetradecanoylphorbol-13-acetate (TPA), estradiol-activated Notch1/ER induced apoptosis during TPA treatment in the transfectant, which was accompanied by the reduced expression of an antiapoptotic molecule Bcl-XL. Even when apoptosis was prevented by the overexpression of Bcl-XL, activated Notch signals still inhibited TPA-induced megakaryocytic differentiation. As for this mechanism, Notch1/recombination signal binding protein J-kappa-induced HES1 but not HES5 was found to inhibit the function of an erythroid/megakaryocytic lineage-specific transcription factor GATA-1. Although HES1 did not affect the DNA binding activity of GATA-1 in gel shift and chromatin immunoprecipitation assays, it directly bound to GATA-1 and dissociated a critical transcriptional cofactor, p300, from GATA-1. Furthermore, overexpressed HES1 inhibited the development of erythroid and megakaryocytic cells in colony assays. Also, the Notch ligand Jagged1 expressed on NIH3T3 cells suppressed the development of erythroid and megakaryocytic cells from cocultured Lin(-)Sca-1(+) hematopoietic stem/progenitor cells. These results suggest that Notch1 inhibits the development of erythroid/ megakaryocytic cells by suppressing GATA-1 activity through HES1.
  • S Nakata; Matsumura, I; H Tanaka; S Ezoe; Y Satoh; J Ishikawa; T Era; Y Kanakura
    JOURNAL OF BIOLOGICAL CHEMISTRY AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC 279 (53) 55578 - 55586 0021-9258 2004/12 [Refereed]
     
    examine the roles for NF-kappaB family proteins in hematopoiesis, we first expressed dominant negative Rel/NF-kappaB (IkappaBSR) in a factor-dependent cell line, Ba/F3. Although IkappaBSR neither affected thrombopoietindependent nor gp130-mediated growth, it suppressed interleukin-3- and erythropoietin-dependent growth at low concentrations. In addition, IkappaBSR enhanced factor-deprived apoptosis through the accumulation of reactive oxygen species (ROS). When expressed in normal hematopoietic stem/progenitor cells, IkappaBSR induced apoptosis even in the presence of appropriate cytokines by accumulating ROS. We also expressed IkappaBSR in an inducible fashion at various stages of hematopoiesis using the OP9 system, in which hematopoietic cells are induced to develop from embryonic stem cells. When IkappaBSR was expressed at the stage of Flk-1(+) cells (putative hemangioblasts), IkappaBSR inhibited the development of primitive hematopoietic progenitor cells by inducing apoptosis through the ROS accumulation. Furthermore, when IkappaBSR was expressed after the development of hematopoietic progenitor cells, it inhibited their terminal differentiation toward erythrocytes, megakaryocytes, and granulocytes by inducing apoptosis through the ROS accumulation. These results indicate that NF-kappaB is required for preventing apoptosis at multiple steps of hematopoiesis by eliminating ROS.
  • 造血幹細胞の自己複製におけるc-Mycの役割
    佐藤 友亮; 松村 到; 田中 宏和; 水木 満佐央; 金倉 譲
    日本血液学会・日本臨床血液学会総会プログラム・抄録集 日本臨床血液学会 66回・46回 788 - 788 2004/09
  • Y Satoh; Matsumura, I; H Tanaka; S Ezoe; H Sugahara; M Mizuki; H Shibayama; E Ishiko; J Ishiko; K Nakajima; Y Kanakura
    JOURNAL OF BIOLOGICAL CHEMISTRY AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC 279 (24) 24986 - 24993 0021-9258 2004/06 
    Notch and HOXB4 have been reported to expand hematopoietic stem cells (HSCs) in vitro. However, their critical effector molecules remain undetermined. We found that the expression of c-myc, cyclin D2, cyclin D3, cyclin E, and E2F1 was induced or enhanced during Notch1- or HOXB4-induced self-renewal of murine HSCs. Since c-Myc can act as a primary regulator of G(1)/S transition, we examined whether c-Myc alone can induce self-renewal of HSCs. In culture with stem cell factor, FLT3 ligand, and IL-6, a 4-hydroxytamoxifen-inducible form of c-Myc (Myc/ERT) enabled murine Lin(-) Sca-1(+) HSCs to proliferate with the surface phenotype compatible with HSCs for more than 28 days. c-Myc activated by 4-hydroxytamoxifen augmented telomerase activities and increased the number of CFU-Mix about 2-fold in colony assays. Also, in reconstitution assays, HSCs expanded by c-Myc could reconstitute hematopoiesis for more than 6 months. As for the mechanism of c-myc induction by Notch1, we found that activated forms of Notch1 (NotchIC) and its downstream effector recombination signal-binding protein-J kappa (RBP-VP16) can activate the c-myc promoter through the element between -195 bp and -161 bp by inducing the DNA-binding complex. Together, these results suggest that c-Myc can support self-renewal of HSCs as a downstream mediator of Notch and HOXB4.
  • S Ezoe; Matsumura, I; Y Satoh; H Tanaka; Y Kanakura
    CELL CYCLE LANDES BIOSCIENCE 3 (3) 314 - 318 1538-4101 2004/03 [Refereed]
     
    Hematopoietic stem cells (HSCs) are characterized by pluripotentiality and a capacity for self-renewal. In order to both maintain a supply of mature blood cells and not to exhaust HSCs throughout the lifespan of the organism, most HSCs remain quiescent and only a limited number enter the cell cycle. In HSCs, the cell cycle is crucially regulated by external factors such as cytokines and interactions with stromal cells and the extracellular matrix (ECM) in the bone marrow (BM) microenvironment. In addition, intrinsic transcription factors expressed in HSCs, including c-Myb, GATA-2, HOX family proteins, and Bmi-1, also control their growth through their effect on gene transcription. In terms of the particular roles in regulation of the cell-cycle, p21(WAF1) (p21) and p27(KIP1) (p27) were shown to maintain the quiescence of HSCs and of progenitor cells, respectively, thereby governing their available pool sizes. Also, p16(INK4A) (p16) and p15(INK4B) ( p15) are thought to act as tumor suppressors, since their inactivation and/or deletion are observable in various types of hematologic malignancies. These results make evident that appropriate cell cycle control, particularly at the early stage of stem/progenitor cells, is required for maintaining normal hematopoiesis.
  • Zhang, X; T Machii; Matsumura, I; S Ezoe; A Kawasaki; H Tanaka; S Ueda; H Sugahara; H Shibayama; M Mizuki; Y Kanakura
    INTERNATIONAL JOURNAL OF HEMATOLOGY SPRINGER TOKYO 77 (3) 263 - 273 0925-5710 2003/04 [Refereed]
     
    Hairy cell leukemia (HCL) is a rare type of chronic B-cell leukemia characterized by the hairy morphology of the leukemia cells. All of 5 HCL samples and an HCL-derived cell line, BNBH-I, showed serrated edges and hairlike projections in May-Grunwald Giemsa stain and protruding actin spikes and lamellipodia in phalloidin stain. These structures were hardly detected on B-cell chronic lymphocytic leukemia (B-CLL) and precursor B-cell acute lymphocytic leukemia (B-ALL) cells. Because Rho guanosine triphosphatases (GTPases) regulate the formation of these structures, we examined the expression levels and activation states of Rho GTPases in HCL cells. RhoA, Rac1, and Cdc42 were overexpressed and constitutively activated in HCL samples and BNBH-I cells but not in B-CLL or precursor B-ALL cells. Next we overexpressed dominant-negative (DN)-RhoA, DN-Rac1, and DN-Cdc42 in BNBH-I. As a result, each DN mutant repressed the growth of BNBH-I cells by more than 50% and inhibited actin spike formation, but only DN-Rac1 suppressed lamellipodia formation. We also found that enforced expression of constitutively active-RhoA, Rac, or Cdc42 in the proB-cell line Ba/F3 was sufficient to induce actin spike formation, whereas none of these molecules produced lamellipodia. These results indicated that constitutively activated Rho GTPases regulate the growth and unique morphology of HCL cells. (C) 2003 The Japanese Society of Hematology.
  • Itaru Matsumura; Hirokazu Tanaka; Yuzuru Kanakura
    CELL CYCLE TAYLOR & FRANCIS INC 2 (4) 333 - 338 1538-4101 2003 [Refereed]
     
    Cell cycle machinery controls not only cell growth but also cell survival and death. For example, overexpression of c-Myc or E2F1, which are involved in G(1)/S transition, causes apoptosis under certain conditions. Furthermore, endogenous E2F1 also participates in apoptosis, as evidenced by the defect of apoptosis in E2F1-deficient mice. Candidate molecules that mediate c-Myc-and E2F1-enhanced apoptosis include p14/p19(ARF), ornithine decarboxylase and lactate degydrogenase-A (for c-Myc) as well as p14/p19(ARF), p73, Apaf-1 and caspase-3 (for E2F1). c-Myc also activates the CD95/Fas-FADD-mediated death signal. c-Myc and E2F1 inhibit NF-kappa B activities induced by TNF alpha or reactive oxygen species. Therefore, c-Myc and E2F1 regulate cell growth and death not only by inducing transcription but also by modulating signal transduction pathways.
  • Molecular mechanisms of E2F1- and c-Myc-enhanced apoptosis
    Matsumura I; Tanaka H; Mizuki M; Sugahara H; Kanakura Y
    Rec. Res. Devel. in Mol. & Cell. Biol. 4:311-324 2003
  • Roles for E2F1 and c-Myc in the regulation of cell growth and survival
    Matsumura I; Tanaka H; Kanakura Y
    Cell Cycle 2:333-338 2003
  • S Ueda; H Ikeda; M Mizuki; J Ishiko; Matsumura, I; H Tanaka; H Shibayama; H Sugahara; E Takai; Zhang, X; T Machii; Y Kanakura
    INTERNATIONAL JOURNAL OF HEMATOLOGY CARDEN JENNINGS PUBL CO LTD 76 (5) 427 - 435 0925-5710 2002/12 
    The c-kit receptor tyrosine kinase (KIT) is constitutively activated by 2 types of naturally occurring mutations, the Val559-->Gly (G559) mutation in the juxtamembrane domain and the Asp814-->Val (V814) mutation in the catalytic domain. We evaluated the effects of the tyrosine kinase inhibitors STI571 and AG1296 on BaF3 cells expressing wild-type KIT (KITWT) or activating mutants of KIT (KITG559 and KITV814) in the presence or absence of the KIT ligand, stem cell factor (SCF). Both STI571 and AG1296 inhibited SCF-dependent activation of KITWT and SCF-independent activation of KITG559 more efficiently, whereas SCF-independent activation of KITV814 was scarcely affected. Furthermore, both inhibitors inhibited SCF-dependent growth of BaF3-KITWT cells and, with higher potencies, SCF-independent growth of BaF3-KITG559 cells through the induction of apoptosis. In contrast, the inhibitors had little or no effect on SCF-independent growth of BaF3-KITV814 cells or on IL-3-dependent growth of BaF3-Mock cells. These results suggested that both inhibitors may be effective therapeutic agents for oncogenic KIT with the juxtamembrane domain mutation, but not with the catalytic domain mutation, and that the activation mechanism of the catalytic domain mutant KIT is complex and entirely different from that of the wild-type KIT or the juxtamembrane domain mutant KIT. (C)2002 The Japanese Society of Hematology.
  • 【p53経路とRB経路 ここまでわかった細胞癌化のメカニズム】 E2F1とMycによるアポトーシス誘導のメカニズム
    松村 到; 田中 宏和; 金倉 譲
    細胞工学 (株)学研メディカル秀潤社 22 (1) 46 - 49 0287-3796 2002/12 
    E2F1とMycによるアポトーシス誘導機構について概説した.一般に,E2F1やMycなどの過剰発現は細胞のアポトーシス感受性を高める.この機構として,E2F1やMycが転写因子としてp19ARFなど種々のアポトーシス促進分子の発現を誘導することが報告されてきた.最近,著者等は,これらの細胞では活性酸素種が蓄積され,更に,過剰なE2F1により抗アポトーシス分子NF-κBの機能が阻害されることにより,細胞のアポトーシス感受性が亢進することを明らかにした
  • H Tanaka; Matsumura, I; S Ezoe; Y Satoh; T Sakamaki; C Albanese; T Machii; RG Pestell; Y Kanakura
    MOLECULAR CELL CELL PRESS 9 (5) 1017 - 1029 1097-2765 2002/05 [Refereed]
     
    Overexpression of c-Myc or E2F1 sensitizes host cells to various types of apoptosis. Here, we found that overexpressed c-Myc or E2F1 induces accumulation of reactive oxygen species (ROS) and thereby enhances serum-deprived apoptosis in NIH3T3 and Saos-2. During serum deprivation, MnSOD mRNA was induced by NF-kappaB in mock-transfected NIH3T3, while this induction was inhibited in NIH3T3 overexpressing c-Myc or E2F1. In these clones, E2F1 inhibited NF-kappaB activity by binding to its subunit p65 in competition with a heterodimeric partner p50. In addition to overexpressed E2F1, endogenous E2F1 released from Rb was also found to inhibit NF-kappaB activity in a cell cycle-dependent manner by using E2F1(+/+) and E2F1(-/-) murine embryonic fibroblasts. These results indicate that E2F1 promotes apoptosis by inhibiting NF-kappaB activity.
  • A Kawasaki; Matsumura, I; J Miyagawa; S Ezoe; H Tanaka; Y Terada; M Tatsuka; T Machii; H Miyazaki; Y Furukawa; Y Kanakura
    JOURNAL OF CELL BIOLOGY ROCKEFELLER UNIV PRESS 152 (2) 275 - 287 0021-9525 2001/01 
    During the late phase of megakaryopoiesis, megakaryocytes undergo polyploidization, which is characterized by DNA duplication without concomitant cell division. However, it remains unknown by which mechanisms this process occurs. AIM-1 and STK15 belong to the Aurora/increase-in-ploidy (Ip1)1 serine/threonine kinase family and play key roles in mitosis. In a human interleukin-3-dependent cell line, F-36P, the expressions of AIM-1 and STK15 mRNA were specifically observed at G2/M phase of the cell cycle during proliferation. In contrast, the expressions of AIM-1 and STK15 were continuously repressed during megakaryocytic polyploidization of human erythro/megakaryocytic cell lines (F-36P, K562, and CMK) treated with thrombopoietin, activated ras (H-ras(G12V)), or phorbol ester. Furthermore, their expressions were suppressed during thrombopoietin-induced polyploidization of normal human megakaryocytes. Activation of AIM-1 by the induced expression of AIM-l(wild-type) canceled TPA-induced polyploidization of K562 cells significantly, whereas that of STK15 did not. Moreover, suppression of AIM-1 by the induced expression of AIM-1 (K/R, dominant-negative type) led to polyploidization in 25% of K562 cells, whereas STK15(K/R) showed no effect. Also, the induced expression of AIM-1(K/R) in CMK cells provoked polyploidization up to 32N. These results suggested that downregulation of AIM-1 at M phase may be involved in abortive mitosis and polyploid formation of megakaryocytes.
  • Matsumura I; Kawasaki A; Tanaka H; Sonoyama J; Ezoe S; Minegishi N; Nakajima K; Yamamoto M; Kanakura Y
    Blood 96 (7) 2440 - 2450 2000/10 [Refereed]
  • J Odajima; Matsumura, I; J Sonoyama; H Daino; A Kawasaki; H Tanaka; N Inohara; T Kitamura; J Downward; K Nakajima; T Hirano; Y Kanakura
    JOURNAL OF BIOLOGICAL CHEMISTRY AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC 275 (31) 24096 - 24105 0021-9258 2000/08 
    Tyrosine kinase oncoproteins cause simultaneous activation of multiple intracellular signaling pathways. However, the precise mechanisms by which individual pathways induce oncogenesis are not well understood. We have investigated the roles of individual signaling pathways in v-Src-dependent cell growth and survival by inhibiting one particular pathway. v-Src induced constitutive activation of signal transducers and activators of transcription 3 (STAT3), phosphatidylinositol 3-kinase, and Res in murine Ba/F3 cells and led to factor-independent proliferation. Dominant-negative mutants of STAT3 (STAT3D) and phosphatidylinositol 3-kinase (Delta p85) inhibited v-Src-dependent growth by similar to 60 and similar to 40%, respectively. Moreover, dominant-negative Res (N17) induced severe apoptosis, which was accompanied by down regulation of Bcl-2 and activation of caspase-3. Although cells overexpressing Bcl-2 or caspase-3 inhibitors remained viable even when N17 was expressed, the growth was reduced by similar to 85%. During N17- and STAT3D-induced growth suppression, expression of cyclin D2, cyclin D3, c-myc, and c-fos was suppressed by N17, whereas that of cyclin D2, cyclin E, and c-myc was suppressed by STAT3D, Thus, v-Src-activated Ras and STAT3 are involved in distinct but partly overlapping transcriptional regulation of cell cycle regulatory molecules. These results suggest that the full oncogenic activity of v-Src requires simultaneous activation of multiple signalings, in which Ras is particularly required for survival.
  • H Daino; Matsumura, I; K Takada; J Odajima; H Tanaka; S Ueda; H Shibayama; H Ikeda; M Hibi; T Machii; T Hirano; Y Kanakura
    BLOOD AMER SOC HEMATOLOGY 95 (8) 2577 - 2585 0006-4971 2000/04 
    The ubiquitin-proteasome pathway is responsible for selective degradation of short-lived cellular proteins and is critical for the regulation of many cellular processes. We previously showed that ubiquitin (Ub) secreted from hairy cell leukemia cells had inhibitory effects on clonogenic growth of normal hematopoietic progenitor cells. In this study, we examined the effects of exogenous Ub on the growth and survival of a series of human hematopoietic cells, including myeloid cell lines (HL-60 and U937), a B-cell line (Daudi), and T-cell lines (KT-3, MT-4, YTC-3, and MOLT-4), Exogenous Ub inhibited the growth of Various hematopoietic cell lines tested, especially of KT-3 and HL-60 cells. The growth-suppressive effects of Ub on KT-3 and HL-60 cells were almost completely abrogated by the proteasome inhibitor PSI or MG132, suggesting the involvement of the proteasome pathway in this process. Furthermore, exogenous Ub evoked severe apoptosis of KT-3 and HL-60 cells through the activation of caspase-3, In interleukin-6 (IL-6)-dependent KT-3 cells, STAT3 was found to be conjugated by exogenous biotinylated Ub and to be degraded in a proteasome-dependent manner, whereas expression levels of STAT1, STAT5, or mitogen-activated protein kinase were not affected. Moreover, IL-6-induced the up-regulation of Bcl-2 and c-myc, and JunB was impaired in Ub-treated KT-3 cells, suggesting that the anti-apoptotic and mitogenic effects of IL-6 were disrupted by Ub, These results suggest that extracellular Ub was incorporated into hematopoietic cells and mediated their growth suppression and apoptosis through proteasome-dependent degradation of selective cellular proteins such as STAT3, (Blood, 2000;95:2577-2585) (C) 2000 by The American Society of Hematology.
  • Tanaka H; Matsumura I; Nakajima K; Daino H; Sonoyama J; Yoshida H; Oritani K; Machii T; Yamamoto M; Hirano T; Kanakura Y
    Blood 95 (4) 1264 - 1273 2000/02 [Refereed]
  • Matsumura, I; H Tanaka; A Kawasaki; J Okajima; H Daino; K Hashimoto; H Wakao; K Nakajima; T Kato; H Miyazaki; Y Kanakura
    JOURNAL OF BIOLOGICAL CHEMISTRY AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC 275 (8) 5553 - 5559 0021-9258 2000/02 
    At the late phase of megakaryocytopoiesis, megakaryocytes undergo endomitosis, which is characterized by DNA replication without cell division. Although a number of cell. cycle regulatory molecules have been identified, the precise roles of these molecules in megakaryocytic endomitosis are largely unknown. In a human interleukin-3-dependent cell line transfected with the thrombopoietin (TPO) receptor c-mpl (F-36P-mpl), either treatment with TPO or the overexpression of activated ras (Ha-Ras(G12V)) induced megakaryocytic maturation with polyploid formation, We found that TPO stimulation or Ha-Ras(G12V) expression led to up-regulation of cyclin D1, cyclin D2, and cyclin D3 expression. In addition, expression levels of cyclin A and cyclin B were reduced during the total course of both TPO- and Ha-Ras(G12V)-induced megakaryocytic differentiation, thereby leading to decreased cdc2 kinase activity. Neither the induced expression of cyclin DI, cyclin D2, or cyclin D3 nor the expression of a dominant negative form of cdc2 alone could induce megakaryocytic differentiation of F-36P-mpl cells. In contrast, overexpression of dominant negative cdc2 together with cyclin D1, cyclin D2, or cyclin D3 facilitated megakaryocytic differentiation in the absence of TPO. These results suggest that both D-type cyclin expression and decreased cdc2 kinase activity may participate in megakaryocytic differentiation.
  • Matsumura, I; T Kitamura; H Wakao; H Tanaka; K Hashimoto; C Albanese; J Downward; RG Pestell; Y Kanakura
    EMBO JOURNAL OXFORD UNIV PRESS 18 (5) 1367 - 1377 0261-4189 1999/03 
    STAT5 is a member of a family of transcription factors that participate in the signal transduction pathways of many hormones and cytokines, Although STAT5 is suggested to play a crucial role in the biological effects of cytokines, its downstream target(s) associated with cell growth control is largely unknown. In a human interleukin-3 (IL-3)-dependent cell line F-36P-mpl, the induced expression of dominant-negative (dn)-STAT5 and of dn-ras led to inhibition of IL-3-dependent cell growth, accompanying the reduced expression of cyclin D1 mRNA. Also, both constitutively active forms of STAT5A (1*6-STAT5A) and ras (H-ras(G12V)) enabled F-36P-mpl cells to proliferate without added growth factors. In NIH 3T3 cells, 1*6-STAT5A and N-ras(G12V) individually and cooperatively transactivated the cyclin D1 promoter in luciferase assays. Both dn-STAT5 and dn-ras suppressed IL-3-induced cyclin D1 promoter activities in F-36P-mpl cells, Using a series of mutant cyclin DI promoters, 1*6-STAT5A was found to transactivate the cyclin D1 promoter through the potential STAT-binding sequence at -481 bp, In electrophoretic mobility shift assays, STAT5 bound to the element in response to IL-3, Furthermore, the inhibitory effect of dn-STAT5 on IL-3-dependent growth was restored by expression of cyclin DI, Thus STAT5, in addition to ras signaling, appears to mediate transcriptional regulation of cyclin D1, thereby contributing to cytokine-dependent growth of hematopoietic cells.
  • SUZUKI Kenichi; TAGAWA Shinichi; KOH Ki-ryang; HINO Masayuki; YAMANE Takahisa; WAKASA Kenichi; SASAKI Masaomi; MIZUKI Masao; AZENISHI Yasuhiko; TANAKA Hirokazu; MACHII Takashi; AOZASA Katsuyuki; OHSAWA Masahiko; SUGANO Yoshiyuki; HARA Junichi; KAWA Keisei; TATSUMI Noriyuki
    臨床病理 44 (10) 927 - 935 0047-1860 1996/10 [Refereed]

Conference Activities & Talks

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    谷口 貴英; 中山 聖子; 森田 泰慶; 頼 晋也; 平瀬 主税; 谷口 康博; 井上 宏昭; 大山 泰世; 三宅 義昭; Espinoza J Luis; 田中 宏和; 辰巳 陽一; 芦田 隆司; 松村 到
    日本リンパ網内系学会会誌  2019/05
  • 治療抵抗性TAFRO症候群に合併したAILTの1例  [Not invited]
    三宅 義昭; 頼 晋也; 井上 宏昭; 口分田 貴裕; 谷口 康博; 中山 聖子; 森田 泰慶; Espinoza J.L; 田中 宏和; 辰巳 陽一; 芦田 隆司; 松村 到
    日本リンパ網内系学会会誌  2019/05
  • ヘモグロビン値と血小板数に基づくびまん性大細胞型B細胞リンパ腫、非特異型の新たな予後指標の提唱  [Not invited]
    中山 聖子; 松田 光弘; 森田 泰慶; 頼 晋也; 谷口 康博; 井上 宏昭; 大山 泰世; 谷口 貴英; 三宅 義昭; 足立 達哉; 末田 早苗; Espinoza J. Luis; 田中 宏和; 辰巳 陽一; 芦田 隆司; 松村 到
    日本リンパ網内系学会会誌  2019/05
  • 十二指腸原発濾胞性リンパ腫における抗腫瘍免疫の寄与  [Not invited]
    井上 宏昭; 頼 晋也; 口分田 貴裕; 芹澤 憲太郎; 谷口 康博; 中山 聖子; 森田 泰慶; Luis Espinoza J; 田中 宏和; 辰巳 陽一; 芦田 隆司; 松村 到
    日本リンパ網内系学会会誌  2019/05
  • 谷口貴英; 中山聖子; 森田泰慶; 頼晋也; 大山泰世; 三宅義昭; 田中宏和; 辰巳陽一; 芦田隆司; 松村到
    臨床血液  2019/01
  • 脳静脈洞血栓症を合併し、開頭減圧術・術後エクリズマブ投与が有効であったPNHの一例(Post-operative treatment with eculizumab for PNH presenting as cerebral venous sinus thrombosis)  [Not invited]
    岩田 吉生; 森田 泰慶; 辻 潔; 頼 晋也; 田崎 貴之; 井上 宏昭; 谷口 康博; 藤本 昂; 田中 宏和; 芦田 隆司; 加藤 天美; 松村 到
    臨床血液  2018/10
  • KMFに登録されたボルテゾミブとIMiDs両剤に抵抗性の再発骨髄腫の予後解析(Clinical outcomes of relapsed myeloma, dual refractory to bortezomib and IMiDs in KMF registry)  [Not invited]
    藤原 亮介; 田中 宏和; 芹澤 憲太郎; 金子 仁臣; 志村 勇司; 太田 健介; 淵田 真一; 中谷 綾; 諫田 淳也; 八木 秀男; 和田 勝也; 小杉 智; 魚嶋 伸彦; 柴山 浩彦; 小原 尚恵; 中谷 英仁; 内山 人二; 足立 陽子; 飯田 正人; 濱田 常義; 松田 光弘; 高折 晃史; 野村 昌作; 島崎 千尋; 日野 雅之; 黒田 純也; 谷脇 雅史; 今田 和典; 金倉 譲; 松村 到
    臨床血液  2018/10
  • 骨髄異形成症候群に合併したSweet病に対するアザシチジンの免疫学的効果(Immunological effects of azacitidin on Sweet's disease associated with myelodysplastic syndromes)  [Not invited]
    谷口 貴英; 芹澤 憲太郎; 田中 宏和; 森田 泰慶; 谷口 康博; 辰巳 陽一; 芦田 隆司; 松村 到
    臨床血液  2018/10
  • 形質細胞腫の後方視的多施設共同研究(関西骨髄腫フォーラム)(Retrospective multi-centers study of plasmacytoma)  [Not invited]
    中谷 綾; 田中 宏和; 八木 秀男; 太田 健介; 柴山 浩彦; 諫田 淳也; 新堂 真紀; 志村 勇司; 小杉 智; 木田 亨; 金子 仁臣; 今田 和典; 烏野 隆博; 松田 光弘; 飯田 正人; 足立 陽子; 淵田 真一; 魚嶋 伸彦; 内山 人二; 高橋 良一; 松井 利充; 和田 勝也; 清田 実希; 島崎 千尋; 日野 雅之; 黒田 純也; 金倉 譲; 高折 晃史; 野村 昌作; 松村 到
    臨床血液  2018/10
  • CD34陽性ヒト骨髄腫幹細胞の同定と特性解析(Identification and characterization of CD34+ myeloma cell population as myeloma-initiating cells)  [Not invited]
    芹澤 憲太郎; 田中 宏和; 福井 彩乃; 藤原 亮介; 佐野 圭吾; 口分田 貴裕; 谷口 康博; 森田 泰慶; ルイス・エスピノザ; 辰巳 陽一; 芦田 隆司; 松村 到
    臨床血液  2018/10
  • 十二指腸型濾胞性リンパ腫は、抗腫瘍免疫により良好な予後を示す(Duodenal-type follicular lymphoma exhibits good prognosis through the increased anti-tumor immunity)  [Not invited]
    井上 宏昭; 頼 晋也; 口分田 貴裕; 芹澤 憲太郎; 谷口 康博; 中山 聖子; 森田 泰慶; ルイス・エスピノザ; 田中 宏和; 辰巳 陽一; 芦田 隆司; 松村 到
    臨床血液  2018/10
  • CLEC-2の発現は巨核球にバイアスした長期骨髄再建能を有する造血幹細胞集団を規定する(CLEC-2 identifies a functionally distinct subpopulation of megakaryocyte-biased HSCs)  [Not invited]
    口分田 貴裕; 田中 宏和; Espinoza J. Luis; 岩田 吉生; 佐野 圭吾; 芹澤 憲太郎; 谷口 康博; 頼 晋也; 森田 泰慶; 辰巳 陽一; 芦田 隆司; 松村 到
    臨床血液  2018/10
  • BCR-ABL陰性骨髄増殖性腫瘍においてTET2変異は生存に対する予後不良因子である(TET2 mutation is a poor prognostic factor for survival in BCR-ABL-negative MPN patients)  [Not invited]
    谷口 康博; 田中 宏和; 藤原 亮介; 森田 泰慶; 花本 仁; 辰巳 陽一; 芦田 隆司; 松村 到
    臨床血液  2018/10
  • RRMM患者に対するKRD療法およびKD療法の後方視的解析(関西骨髄腫フォーラム)(KRD and KD treatment for relapsed/refractory multiple myeloma in Kansai Myeloma Forum study)  [Not invited]
    恩田 佳幸; 諫田 淳也; 金子 仁臣; 柴山 浩彦; 志村 勇司; 太田 健介; 田中 宏和; 淵田 真一; 中谷 綾; 魚嶋 伸彦; 小杉 智; 松田 光弘; 足立 陽子; 八木 秀男; 内山 人二; 新堂 真紀; 今田 和典; 日野 雅之; 野村 昌作; 島崎 千尋; 黒田 純也; 金倉 譲; 高折 晃史; 松村 到
    臨床血液  2018/10
  • 症候性骨髄腫1414例の後方視的解析 関西骨髄腫フォーラムからの最新報告(Retrospective analyses of 1,414 symptomatic multiple myeloma cases: update from Kansai Myeloma Forum)  [Not invited]
    田中 宏和; 芹澤 憲太郎; 中谷 綾; 金子 仁臣; 太田 健介; 小杉 智; 八木 秀男; 花本 仁; 淵田 真一; 志村 勇司; 柴山 浩彦; 小原 尚恵; 中谷 英仁; 諫田 淳也; 魚嶋 伸彦; 和田 勝也; 烏野 隆博; 松井 利充; 内山 人二; 松田 光弘; 足立 陽子; 高折 晃史; 黒田 純也; 谷脇 雅史; 島崎 千尋; 日野 雅之; 今田 和典; 野村 昌作; 金倉 譲; 松村 到
    臨床血液  2018/10
  • サリドマイド単剤治療を施行した症候性骨髄腫230例の後方視的解析 関西骨髄腫フォーラム(Analysis of 230 cases of thalidomide monotherapy for symptomatic myeloma registered in KMF)  [Not invited]
    金子 仁臣; 柴山 浩彦; 八木 秀男; 諫田 淳也; 中谷 綾; 小杉 智; 木田 亨; 田中 宏和; 志村 勇司; 淵田 真一; 足立 陽子; 和田 勝也; 清田 実希; 魚嶋 伸彦; 太田 健介; 小原 尚恵; 濱田 常義; 小林 正行; 内山 人二; 烏野 隆博; 黒田 純也; 今田 和典; 高折 晃史; 島崎 千尋; 金倉 譲; 日野 雅之; 野村 昌作; 松村 到
    臨床血液  2018/10
  • 異常なRTKの細胞内輸送阻害は急性骨髄性白血病における有望な治療標的である(Intracellular trafficking of mutated RTKs shows promising therapeutic target against AML)  [Not invited]
    頼 晋也; 田中 宏和; 鈴木 麻衣; Espinoza Luis; 谷村 朗; 森田 泰慶; 辰巳 陽一; 横田 貴史; 織谷 健司; 渡邊 俊雄; 金倉 譲; 松村 到
    臨床血液  2018/10
  • 山田枝里佳; 斉藤花往里; 藤本昂; 角谷宏明; 岩田吉生; 谷口貴英; 源周治; 大山泰世; 口分田貴裕; 井上宏昭; 芹澤憲太郎; 谷口康博; 頼晋也; 平瀬主税; 森田泰慶; 田中宏和; 岡野意浩; 坂田尚己; 芦田隆司; 松村到
    日本アフェレシス学会雑誌  2018/10
  • The evaluation of consolidation and maintenance therapies after HDT/ASCT for symptomatic MM  [Not invited]
    Aya Nakaya; Eiji Nakatani; Hitomi Kaneko; Hirohiko Shibayama; Yuji Shimura; Junya Kanda; Maki Shindo; Kensuke Ohta; Satoru Kosugi; Shin-Ichi Fuchida; Hideo Yagi; Hirokazu Tanaka; Yuri Kamitsuji; Takahiro Karasuno; Nobuhiko Uoshima; Eri Kawata; Yoko Adachi; Hitoji Uchiyama; Toshimitsu Matsui; Mitsuhiro Matsuda; Jun Ishikawa; Tsuneyoshi Hamada; Ryoichi Takahashi; Kazunori Imada; Chihiro Shimazaki; Masayuki Hino; Junya Kuroda; Yuzuru Kanakura; Akifumi Takaori-Kondo; Shosaku Nomura; Itaru Matsumura
    BONE MARROW TRANSPLANTATION  2018/09  NATURE PUBLISHING GROUP
  • 三宅 義昭; 口分田 貴裕; 波江野 高大; 森田 泰慶; 嶋田 高広; 田中 宏和; 辰巳 陽一; 芦田 隆司; 松村 到
    臨床血液  2018/02
  • 國田 裕貴; 口分田 貴裕; 波江野 高大; 森田 泰慶; 嶋田 高広; 田中 宏和; 辰巳 陽一; 芦田 隆司; 松村 到
    臨床血液  2018/02
  • 口分田貴裕; 波江野高大; 齋藤花往里; 佐野圭吾; 谷口康博; 森田泰慶; 田中宏和; 辰巳陽一; 芦田隆司; 松村到
    日本臨床腫瘍学会学術集会(CD-ROM)  2018
  • 小森舞子; 井上宏昭; 角谷宏明; 大山泰世; 口分田貴裕; 森田泰慶; 田中宏和; 芦田隆司; 田崎貴之; 奥田武司; 松村到
    日本造血細胞移植学会総会プログラム・抄録集  2017/12
  • 波江野 高大; 頼 晋也; 藤本 昂; 森田 泰慶; 田中 宏和; 辰巳 陽一; 芦田 隆司; 松村 到
    臨床血液  2017/01
  • 堀川 亮太; 頼 晋也; 齋藤 花往里; 森田 泰慶; 田中 宏和; 辰巳 陽一; 芦田 隆司; 松村 到
    臨床血液  2017/01
  • 太田健介; 山村亮介; 田中宏和; 柴山浩彦; 小原尚恵; 中谷綾; 小杉智; 木田亨; 淵田真一; 新堂真紀; 小林正行; 黒田純也; 金子仁臣; 魚嶋伸彦; 上辻由里; 松田光弘; 高橋隆幸; 浜田常義; 中谷英仁; 今田和典; 島崎千尋; 谷脇雅史; 野村昌作; 日野雅之; 松村到; 金倉譲; 高折(近藤)晃史
    臨床血液  2016/09
  • 芹澤憲太郎; 森田泰慶; 口分田貴裕; 田中宏和; 山田枝里佳; 芦田隆司; 芦田隆司; 松村到
    日本輸血細胞治療学会誌  2016/04
  • 藤本昂; 頼晋也; 岩田吉生; 平瀬主税; 森田泰慶; 田中宏和; 辰巳陽一; 芦田隆司; 松村到
    臨床血液  2016/02
  • 吉川智恵; 芹澤憲太郎; 森田泰慶; 田中宏和; 辰巳陽一; 芦田隆司; 松村到
    臨床血液  2016/02
  • 齋藤花往里; 頼晋也; 岩田吉生; 田中宏和; 辰巳陽一; 芦田隆司; 松村到; 柳原緑; 大磯直毅; 川田暁
    臨床血液  2016/02
  • 柳原緑; 成田智彦; 大磯直毅; 川田暁; 岩田吉生; 田中宏和; 松村到
    日本皮膚科学会雑誌  2016/01
  • 金子仁臣; 金子仁臣; 八木秀男; 八木秀男; 小原尚恵; 小原尚恵; 柴山浩彦; 柴山浩彦; 田中宏和; 田中宏和; 淵田真一; 淵田真一; 木田亨; 木田亨; 小杉智; 小杉智; 黒田純也; 黒田純也; 太田健介; 太田健介; 新堂真紀; 新堂真紀; 小林正行; 小林正行; 上辻由里; 中谷綾; 足立陽子; 河田英里; 内山人二; 魚嶋伸彦; 浦瀬文明; 高橋隆幸; 高橋良一; 飯田正人; 松村到; 松村到; 日野雅之; 金倉譲; 金倉譲; 島崎千尋
    臨床血液  2015/09
  • Hirokazu Tanaka; Shinya Rai; Toshio Watazzabe; Yuzuru Kanakura; Itaru Matsumura
    EXPERIMENTAL HEMATOLOGY  2015/09  ELSEVIER SCIENCE INC
  • Shinya Rai; Hirokazu Tanaka; Toshio Watanabe; Yuzuru Kanakura; Itaru Matsumura
    EXPERIMENTAL HEMATOLOGY  2015/09  ELSEVIER SCIENCE INC
  • 口分田貴裕; 岩田吉夫; 谷口貴秀; 源周治; 大山泰世; 佐野圭吾; 川内超矢; 芹澤憲太郎; 谷口康博; 頼晋也; 金井良高; 平瀬主税; 森田泰慶; 田中宏和; 宮武淳一; 辰巳陽一; 芦田隆司; 松村到
    日本造血細胞移植学会総会プログラム・抄録集  2015/02
  • 宮武淳一; 岩田吉生; 谷口貴英; 源周治; 大山泰世; 川内超矢; 佐野圭吾; 口分田貴裕; 芹澤憲太郎; 谷口康博; 頼晋也; 金井良高; 平瀬主税; 森田泰慶; 田中宏和; 辰巳陽一; 芦田隆司; 松村到
    日本造血細胞移植学会総会プログラム・抄録集  2015/02
  • 芹澤憲太郎; 森田泰慶; 谷口貴英; 岩田吉生; 源周治; 大山泰世; 川内超矢; 金井良高; 頼晋也; 平瀬主税; 田中宏和; 宮武淳一; 辰巳陽一; 芦田隆司; 松村到
    日本造血細胞移植学会総会プログラム・抄録集  2015/02
  • 芹澤憲太郎; 森田泰慶; 江本正克; 大山泰世; 福井彩乃; 井上宏昭; 川内超矢; 金井良高; 平瀬主税; 田中宏和; 嶋田高広; 宮武淳一; 辰巳陽一; 芦田隆司; 松村到
    日本造血細胞移植学会総会プログラム・抄録集  2014/02
  • Efficacy of early intervention of deferasirox in patients with transfusional iron overload  [Not invited]
    芦田 隆司; 丸瀬ちほ; 福島靖幸; 川野亜美; 山田枝里佳; 井手大輔; 菅野知恵美; 加藤祐子; 椿本祐子; 伊藤志保; 峯 佳子; 藤田往子; 金光 靖; 森嶋祥之; 森田 泰慶; 田中 宏和; 嶋田 高広; 宮武 淳一; 辰巳 陽一; 松村 到
    第75回日本血液学会学術集会  2014  札幌  第75回日本血液学会学術集会
  • T-cell/histio-rich large B-cell lymphoma  [Not invited]
    福井 彩乃; 平瀨 主税; 江本 正克; 森田 泰慶; 田中 宏和; 嶋田 高広; 宮武 淳一; 辰巳 陽一; 芦田 隆司; 松村 到
    第202回日本内科学会近畿地方会  2013/12  大阪  第202回日本内科学会近畿地方会
  • Hirokazu Tanaka; Satoru Kosugi; Toru Kida; Kensuke Ohta; Ryosuke Yamamura; Hirohiko Shibayama; Takae Kohara; Hitomi Kaneko; Shin-ichi Fuchida; Masayuki Kobayashi; Kazue Miyamoto; Maki Shindo; Junya Kuroda; Nobuhiko Uoshima; Yayoi Matsumura; Yumi Yoshii; Yuri Kamitsuji; Shogen Boku; Kazuyoshi Ishii; Mitsuhiro Matsuda; Takayuki Takahashi; Tsuneyoshi Hamada; Yoko Adachi; Eiji Nakatani; Shosaku Nomura; Masafumi Taniwaki; Akifumi Takaori; Chihiro Shimazaki; Mitsuru Tsudo; Masayuki Hino; Itaru Matsumura; Yuzuru Kanakura
    BLOOD  2013/11  AMER SOC HEMATOLOGY
  • 生体内に残存するCML幹細胞の特性解析  [Not invited]
    田中 宏和; 松村 到
    新学術領域研究 第7回総括班会議  2013/11  福岡  新学術領域研究 第7回総括班会議
  • Trib1およびTrib2はAKTのリン酸化を抑制することで骨髄系への分化を抑制する(Trib1 and Trib2 block myeloid differentiation by suppressing AKT phosphorylation)  [Not invited]
    金井 良高; 嶋田 高広; 田中 宏和; 松村 到
    日本癌学会総会記事  2013/10
  • Trib１and Trib2 block myeloid differentitation by sippressing AKT phosphorylation  [Not invited]
    金井 良高; 嶋田 高広; 谷口 康博; 賴 晋也; 平瀨 主税; 森田 泰慶; 田中 宏和; 宮武 淳一; 辰巳 陽一; 芦田 隆司; 松村 到
    第75回日本血液学会学術集会  2013/10  札幌  第75回日本血液学会学術集会
  • CALM controls signaling RTKs by regulating their cellular localization in hematopoietic cells  [Not invited]
    賴 晋也; 田中 宏和; 松村 到; Mai Suzuki; Toshio Watanabe; 谷村 朗; 松井敬子; 金倉 譲
    第75回日本血液学会学術集会  2013/10  札幌  第75回日本血液学会学術集会
  • Clinical outcome of radioimmunotherapy with ASCT(Z-LEED) for B-cell Lymphoma  [Not invited]
    辰巳 陽一; 賴 晋也; 金井 良高; 平瀨 主税; 山口 晃史; 森田 泰慶; 田中 宏和; 嶋田 高広; 宮武 淳一; 芦田 隆司
    第75回日本血液学会学術集会  2013/10  札幌  第75回日本血液学会学術集会
  • Trib 1 and 2 block myeloid differentation by suppressung AKT phosphorylation  [Not invited]
    金井 良高; 嶋田 高広; 田中 宏和; 松村 到
    第72回 日本癌学会学術集会  2013/10  横浜  第72回 日本癌学会学術集会
  • Results of gemcitabine therapy for related of refractory Non-Hodgkin’slymphoma in one institute  [Not invited]
    芹澤 憲太郎; 森田 泰慶; 谷口 康博; 川内 超矢; 江口 剛; 江本 正克; 金井 良高; 賴 晋也; 平瀨 主税; 田中 宏和; 口分田 貴裕; 宮武 淳一; 辰巳 陽一; 芦田 隆司; 松村 到
    第75回日本血液学会学術集会  2013/10  札幌  第75回日本血液学会学術集会
  • CALM links cytokine to hematopoietic cell growth and survival by regulating intracellulartrafficking of receptor tyrosune kinases  [Not invited]
    賴 晋也; 田中 宏和; 松村 到; Mai Suzuki; Toshio Watanabe; 谷村 朗; 松井敬子; 金倉 譲
    第18回 欧州血液学会 EHA  2013/06  ストックホルム  第18回 欧州血液学会 EHA
  • 芹澤憲太郎; 綿谷陽作; 谷口康博; 森田泰慶; 川内超矢; 江本正克; 平瀬主税; 田中宏和; 嶋田高広; 川西一信; 宮武淳一; 辰巳陽一; 芦田隆司; 松村到
    日本造血細胞移植学会総会プログラム・抄録集  2013/02
  • 川西一信; 綿谷陽作; 谷口康博; 川内超矢; 芹澤憲太郎; 江本正克; 金井良高; 頼晋也; 平瀬主税; 森田泰慶; 田中宏和; 嶋田高広; 宮武淳一; 辰巳陽一; 芦田隆司; 松村到
    日本造血細胞移植学会総会プログラム・抄録集  2013/02
  • CLINICAL OUTCOME OF RADIOIMMUNOTHERAPY WITH ASCT (Z-LEED) FOR RELAPSED AND REFRACTORY B-CELL LYMPHOMA  [Not invited]
    Y. Tatsumi; S. Rai; Y. Kanai; C. Hirase; T. Yamaguchi; Y. Morita; H. Tanaka; T. Simada; K. Kawanishi; J. Miyaktake; T. Ashida; I. Matsumura
    ANNALS OF ONCOLOGY  2012/10  OXFORD UNIV PRESS
  • Efficacy and safety of both 5-azacitidine and deferasirox treatment in myelodysplastic syndrome  [Not invited]
    芦田 隆司; 森田 泰慶; 辰巳 陽一; 川野亜美; 山田枝里佳; 井出大輔; 菅野知恵美; 加藤祐子; 椿本祐子; 伊藤志保; 峯 佳子; 藤田往子; 金光 靖; 森嶋祥之; 田中 宏和; 嶋田 高広; 川西一信; 宮武 淳一; 松村 到
    第74回日本血液学会学術集会  2012/10  京都  第74回日本血液学会学術集会
  • Bioclonal acute myeloid leukemia with t(2;5;15)and ｔ（9;22)  [Not invited]
    芹澤 憲太郎; 綿谷 陽作; 大山 泰世; 江本 正克; 大山 雄一; 谷口 康博; 金井 良高; 頼 晋也; 平瀬 主税; 山口 晃史; 森田 泰慶; 田中 宏和; 嶋田 高広; 川西一信; 辰巳 陽一; 芦田 隆司; 松村 到
    第74回日本血液学会学術集会  2012/10  京都  第74回日本血液学会学術集会
  • Idenfication and characterization of acute myeloid leukemistem cells by singlcell genexpression profile  [Not invited]
    田中 宏和; 松村 到; 秋丸 裕司; 金倉 譲
    第１０回日本臨床腫瘍学会学術集会  2012/07  大阪  第１０回日本臨床腫瘍学会学術集会
  • Clinical outcome of radioimmunotherapy with ASCT (Z-LEED)for relapsed and refractory B- cell lymphoma  [Not invited]
    辰巳 陽一; 賴 晋也; 金井 良高; 平瀨 主税; 山口 晃史; 森田 泰慶; 田中 宏和; 嶋田 高広; 川西 一信; 宮武 淳一; 芦田 隆司; 松村 到
    第10回日本臨床腫瘍学会学術集会  2012/07  大阪  第10回日本臨床腫瘍学会学術集会
  • 造血器腫瘍関連遺伝子異常が樹状細胞分化に及ぼす影響の解析  [Not invited]
    藤田 二郎; 水木 満佐央; 大塚 正恭; 江副 幸子; 佐藤 友亮; 福島 健太郎; 徳永 正浩; 田中 宏和; 松村 到; 金倉 譲
    Cytometry Research  2012/06  (一社)日本サイトメトリー学会
  • 単一細胞遺伝子発現プロファイルを用いた白血病幹細胞の同定とその特性  [Not invited]
    田中 宏和; 松村 到; 秋丸 裕司
    第２２回日本サイトメトリー学会  2012/06  大阪  第２２回日本サイトメトリー学会
  • Identiification and characterization of speciffic surface molecules expressed on residual chronic myeloid leukemia stem cell during TKI therapy  [Not invited]
    田中 宏和; 松村 到
    第10回幹細胞シンポジウム  2012/05  兵庫  第10回幹細胞シンポジウム
  • 真性多血症から移行した急性赤白血病に対して非血縁者間骨髄移植が有効であった１例  [Not invited]
    芹澤 憲太郎; 川西 一信; 大山 泰世; 尾嶋 真由子; 井上 宏昭; 口分田 貴裕; 江本 正克; 谷口 康博; 金井 良高; 賴 晋也; 笹川淳; 平瀨 主税; 山口 晃史; 森田 泰慶; 田中 宏和; 嶋田 高広; 辰巳 陽一; 芦田 隆司; 松村 到
    第34回日本造血細胞移植学会総会  2012/02  大阪  第34回日本造血細胞移植学会総会
  • 急性リンパ性白血病寛解導入療法が著効した芽球性形質細胞様樹状細胞腫瘍の1症例  [Not invited]
    井上 明日圭; 芹澤 憲太郎; 川西 一信; 山口 晃史; 森田 泰慶; 田中 宏和; 嶋田 高広; 辰巳 陽一; 芦田 隆司; 松村 到
    臨床血液  2012/01  (一社)日本血液学会-東京事務局
  • Experience of indolent malignant lymphoma treated with Bendamustine in our institute  [Not invited]
    谷口 康博; 辰巳 陽一; 川内 超矢; 江本 正克; 頼 晋也; 金井 良高; 平瀬 主税; 森田 泰慶; 田中 宏和; 芹澤 憲太郎; 嶋田 高広; 川西一信; 宮武 淳一; 芦田 隆司; 松村 到
    第74回日本血液学会学術集会  2012  京都  第74回日本血液学会学術集会
  • An Anti-Apoptotic Molecule, Anamorsin, Functions in Both Iron-Sulfur Protein Assembly and Cellular Iron Homeostasis  [Not invited]
    Akira Tanimura; Yuri Kondo; Hirokazu Tanaka; Itaru Matsumura; Tomohiko Ishibashi; Takao Sudo; Yusuke Satoh; Takafumi Yokota; Sachiko Ezoe; Kenji Oritani; Hirohiko Shibayama; Yuzuru Kanakura
    BLOOD  2011/11  AMER SOC HEMATOLOGY
  • Analysis of iron overload in patients with transfusion-dependent hematological diseases  [Not invited]
    芦田 隆司; 川野亜美; 山田枝里佳; 井手大輔; 菅野知恵美; 加藤祐子; 椿本祐子; 伊藤志保; 峯 佳子; 藤田往子; 金光 靖; 森嶋祥之; 大山 泰世; 尾嶋 真由子; 井上 宏昭; 口分田 貴裕; 芹澤 憲太郎; 江本 正克; 谷口 康博; 田中 宏和; 金井 良高; 賴 晋也; 笹川 淳; 平瀨 主税; 山口 晃史; 森田 泰慶; 嶋田 高広; 川西 一信; 辰巳 陽一; 松村 到
    第73回日本血液学会学術集会  2011/10  名古屋  第73回日本血液学会学術集会
  • A Cell-Death-Defying Factor, Anamorsin, Contributes Cell Growth through Binding with PICOT and Inactivation of PKCs and p38MAPK  [Not invited]
    Hirohiko Shibayama; Yuri Saito; Akira Tanimura; Hirokazu Tanaka; Itaru Matsumura; Yuzuru Kanakura
    BLOOD  2010/11  AMER SOC HEMATOLOGY
  • A Chromatin Modifier SATB1 Promotes Lymphocyte Production From Primitive Hematopoietic Stem/Progenitor Cells  [Not invited]
    Yusuke Satoh; Takafumi Yokota; Hirokazu Tanaka; Koichi Kokame; Toshiyuki Miyata; Itaru Matsumura; Kenji Oritani; Yuzuru Kanakura
    BLOOD  2010/11  AMER SOC HEMATOLOGY
  • 活性化RasシグナルはBcr-Ablの下流でp21CIP1/WAF1を介して赤芽球造血を抑制する(The activated Ras signal suppresses erythropoiesis downstream of Bcr-Abl by inducing p21CIP1/WAF1)  [Not invited]
    徳永 正浩; 江副 幸子; 田中 宏和; 佐藤 友亮; 松村 到; 金倉 譲
    日本癌学会総会記事  2010/08
  • 抗細胞死分子アナモルシンは、p38MAPKを不活化し細胞増殖をもたらす(A cell-death-defying factor, anamorsin, yields cell growth through inactivation of p38 MAPK)  [Not invited]
    斉藤 有理; 柴山 浩彦; 田中 宏和; 谷村 朗; 松村 到; 金倉 譲
    日本癌学会総会記事  2010/08
  • 生体内鉄過剰が正常造血ならびに造血器腫瘍の発症、進展に及ぼす影響についての解析(Effects of iron-overload on normal hematopoiesis and disease progression of myeloid malignancies)  [Not invited]
    田中 宏和; 松村 到; 佐藤 友亮; 金倉 譲
    日本癌学会総会記事  2010/08
  • 造血器腫瘍の病態 治療の新展開 AML幹細胞の特性解析(Hematopoietic organ tumor: new aspects of its treatment Characterization of AML stem cells)  [Not invited]
    松村 到; 田中 宏和
    日本癌学会総会記事  2010/08
  • 非炎症状態の樹状細胞分化における白血病関連遺伝子異常の役割(Leukemia-related gene abnormalities affect steady-state dendritic cell differentiation)  [Not invited]
    藤田 二郎; 水木 満佐央; 江副 幸子; 田中 宏和; 佐藤 友亮; 福島 健太郎; 徳永 正浩; 松村 到; 金倉 譲
    日本癌学会総会記事  2010/08
  • SIRT1 Deficiency Suppresses the Maintenance of Hematopoietic Stem Cell Pool.  [Not invited]
    Sachiko Ezoe; Itaru Matsumura; Hirokazu Tanaka; Yusuke Satoh; Takafumi Yokota; Kenji Oritani; Yuzuru Kanakura
    BLOOD  2008/11  AMER SOC HEMATOLOGY
  • Roles for the AML1/RUNX1 Point Mutation in the Pathogenesis of MDS/AML  [Not invited]
    Yusuke Satoh; Itarit Matsurnura; Hirokazu Tanaka; Takafumi Yokota; Sachiko Ezoe; Kenji Oritani; Yuzuru Kanakura
    BLOOD  2008/11  AMER SOC HEMATOLOGY
  • 腫瘍性チロシンキナーゼによる病型決定機構 FIP1L1/PDGFRαによる好酸球系細胞への選択的誘導  [Not invited]
    福島 健太郎; 松村 到; 江副 幸子; 佐藤 友亮; 水木 満佐央; 田中 宏和; 織谷 健司; 金倉 譲
    臨床血液  2007/09  (一社)日本血液学会-東京事務局
  • FIP1L1/PDGFRaは造血幹細胞/前駆細胞の好酸球系への分化を誘導する(FIP1L1/PDGFRa imposes commitment towards eosinophic lineage on hematopoietic stem/progenitor cells)  [Not invited]
    福島 健太郎; 松村 到; 江副 幸子; 佐藤 友亮; 安見 正人; 田中 宏和; 金倉 譲
    日本癌学会総会記事  2007/08  日本癌学会
  • NAD-dependent histone deacetylase, SIRT1, plays essential roles in the maintenance of hematopoietic stem cells.  [Not invited]
    Sachiko Ezoe; Itaru Matsumura; Hirokazu Tanaka; Hirohiko Shibayama; Masao Mizuki; Yuzuru Kanakura
    BLOOD  2006/11  AMER SOC HEMATOLOGY
  • GSK3-β阻害剤が造血幹/前駆細胞の増殖、分化に及ぼす影響についての検討  [Not invited]
    田中 宏和; 松村 到; 伊藤 仁也; 多田 典子; 中畑 龍俊; 金倉 譲
    臨床血液  2006/09  (一社)日本血液学会-東京事務局
  • AML1のC端欠失変異体が造血幹/前駆細胞に及ぼす影響についての解析  [Not invited]
    佐藤 友亮; 松村 到; 田中 宏和; 江副 幸子; 金倉 譲
    日本癌学会総会記事  2005/09  日本癌学会
  • AML1のC端欠失変異体が造血幹/前駆細胞に及ぼす影響についての解析  [Not invited]
    佐藤 友亮; 松村 到; 田中 宏和; 江副 幸子; 金倉 譲
    日本血液学会・日本臨床血液学会総会プログラム・抄録集  2005/09  日本臨床血液学会

MISC

  • 田中宏和; 芹澤憲太郎; 松村到  月刊血液内科  84-  (4)  2022
  • 口分田貴裕; 頼晋也; 波江野高大; 角谷宏明; 源周治; 綿谷陽作; 芹澤憲太郎; 谷口康博; 森田泰慶; 田中宏和; 芦田隆司; 松村到  日本造血細胞移植学会総会プログラム・抄録集  43rd-  2021
  • 谷口康博; 平瀬主税; 芦田隆司; 波江野高大; 角谷宏明; 源周治; 綿谷陽作; 口分田貴裕; 芹澤憲太郎; 頼晋也; 森田泰慶; 田中宏和; 辰巳陽一; 松村到  日本造血細胞移植学会総会プログラム・抄録集  43rd-  2021
  • 角谷宏明; 口分田貴裕; 源周治; 頼晋也; 森田泰慶; 田中宏和; 芦田隆司; 松村到  臨床血液  62-  (3)  2021
  • Aya Nakaya; Takae Kohara; Hirohiko Shibayama; Yoshiyuki Onda; Junya Kanda; Hitomi Kaneko; Kazunori Imada; Toru Kida; Satoru Kosugi; Jun Ishikawa; Ryosuke Yamamura; Yutaka Shimazu; Hirokazu Tanaka; Shin-Ichi Fuchida; Yuji Shimura; Miki Kiyota; Katsuya Wada; Tomoki Ito; Nobuhiko Uoshima; Hideo Yagi; Satoshi Yoshihara; Kensuke Ohta; Chihiro Shimazaki; Masayuki Hino; Akifumi Takaori-Kondo; Junya Kuroda; Itaru Matsumura; Yuzuru Kanakura; Shosaku Nomura  BONE MARROW TRANSPLANTATION  55-  (SUPPL 1)  560  -561  2020/12
  • 谷口康博; 芦田隆司; 森田泰慶; 平瀬主税; 頼晋也; 中山聖子; 芹澤憲太郎; 口分田貴裕; 井上宏昭; 岩田吉男; 谷口貴英; 源周治; 角谷宏明; 藤本昂; 小森舞子; 波江野高大; 三宅義昭; 辰巳陽一; 田中宏和; 松村到  日本造血細胞移植学会総会プログラム・抄録集  42nd-  2020
  • 脳静脈洞血栓症を合併し、開頭減圧術・術後エクリズマブ投与が有効であったPNHの一例(Post-operative treatment with eculizumab for PNH presenting as cerebral venous sinus thrombosis)
    岩田 吉生; 森田 泰慶; 辻 潔; 頼 晋也; 田崎 貴之; 井上 宏昭; 谷口 康博; 藤本 昂; 田中 宏和; 芦田 隆司; 加藤 天美; 松村 到  臨床血液  59-  (9)  1765  -1765  2018/09
  • KMFに登録されたボルテゾミブとIMiDs両剤に抵抗性の再発骨髄腫の予後解析(Clinical outcomes of relapsed myeloma, dual refractory to bortezomib and IMiDs in KMF registry)
    藤原 亮介; 田中 宏和; 芹澤 憲太郎; 金子 仁臣; 志村 勇司; 太田 健介; 淵田 真一; 中谷 綾; 諫田 淳也; 八木 秀男; 和田 勝也; 小杉 智; 魚嶋 伸彦; 柴山 浩彦; 小原 尚恵; 中谷 英仁; 内山 人二; 足立 陽子; 飯田 正人; 濱田 常義; 松田 光弘; 高折 晃史; 野村 昌作; 島崎 千尋; 日野 雅之; 黒田 純也; 谷脇 雅史; 今田 和典; 金倉 譲; 松村 到  臨床血液  59-  (9)  1739  -1739  2018/09
  • 症候性骨髄腫1414例の後方視的解析 関西骨髄腫フォーラムからの最新報告(Retrospective analyses of 1,414 symptomatic multiple myeloma cases: update from Kansai Myeloma Forum)
    田中 宏和; 芹澤 憲太郎; 中谷 綾; 金子 仁臣; 太田 健介; 小杉 智; 八木 秀男; 花本 仁; 淵田 真一; 志村 勇司; 柴山 浩彦; 小原 尚恵; 中谷 英仁; 諫田 淳也; 魚嶋 伸彦; 和田 勝也; 烏野 隆博; 松井 利充; 内山 人二; 松田 光弘; 足立 陽子; 高折 晃史; 黒田 純也; 谷脇 雅史; 島崎 千尋; 日野 雅之; 今田 和典; 野村 昌作; 金倉 譲; 松村 到  臨床血液  59-  (9)  1510  -1510  2018/09
  • 腹水貯留にて発症したprimary effusion lymphoma-like diffuse large B-cell lymphomaの1例
    堀川 亮太; 頼 晋也; 齋藤 花往里; 森田 泰慶; 田中 宏和; 辰巳 陽一; 芦田 隆司; 松村 到  臨床血液  58-  (1)  48  -48  2017/01
  • 副腎不全を契機に診断した両側性副腎原発悪性リンパ腫の1例
    波江野 高大; 頼 晋也; 藤本 昂; 森田 泰慶; 田中 宏和; 辰巳 陽一; 芦田 隆司; 松村 到  臨床血液  58-  (1)  53  -53  2017/01
  • 太田健介; 山村亮介; 田中宏和; 柴山浩彦; 小原尚恵; 中谷綾; 小杉智; 木田亨; 淵田真一; 新堂真紀; 小林正行; 黒田純也; 金子仁臣; 魚嶋伸彦; 上辻由里; 松田光弘; 高橋隆幸; 浜田常義; 中谷英仁; 今田和典; 島崎千尋; 谷脇雅史; 野村昌作; 日野雅之; 松村到; 金倉譲; 高折(近藤)晃史  臨床血液  57-  (9)  1533  -1533  2016/09
  • CLLの経過中に発症したHodgkin variant of Richter syndromeの1例
    藤本 昂; 頼 晋也; 岩田 吉生; 平瀬 主税; 森田 泰慶; 田中 宏和; 辰巳 陽一; 芦田 隆司; 松村 到  臨床血液  57-  (2)  187  -187  2016/02
  • 同種造血幹細胞移植後に再発した骨髄異形成症候群(MDS)におけるAzacitidine(AZA)療法
    吉川 智恵; 芹澤 憲太郎; 森田 泰慶; 田中 宏和; 辰巳 陽一; 芦田 隆司; 松村 到  臨床血液  57-  (2)  190  -191  2016/02
  • 孤発性皮膚myeloid sarcomaの1例
    齋藤 花往里; 頼 晋也; 岩田 吉生; 田中 宏和; 辰巳 陽一; 芦田 隆司; 松村 到; 柳原 緑; 大磯 直毅; 川田 暁  臨床血液  57-  (2)  197  -198  2016/02
  • 造血器腫瘍関連遺伝子異常が樹状細胞分化に及ぼす影響の解析
    藤田 二郎; 水木 満佐央; 大塚 正恭; 江副 幸子; 佐藤 友亮; 福島 健太郎; 徳永 正浩; 田中 宏和; 松村 到; 金倉 譲  Cytometry Research  22-  (Suppl.)  65  -65  2012/06
  • 急性リンパ性白血病寛解導入療法が著効した芽球性形質細胞様樹状細胞腫瘍の1症例
    井上 明日圭; 芹澤 憲太郎; 川西 一信; 山口 晃史; 森田 泰慶; 田中 宏和; 嶋田 高広; 辰巳 陽一; 芦田 隆司; 松村 到  臨床血液  53-  (1)  116  -116  2012/01
  • 田中 宏和; 金倉 譲  臨床検査  55-  (5)  507  -511  2011/05
  • 活性化RasシグナルはBcr-Ablの下流でp21CIP1/WAF1を介して赤芽球造血を抑制する(The activated Ras signal suppresses erythropoiesis downstream of Bcr-Abl by inducing p21CIP1/WAF1)
    徳永 正浩; 江副 幸子; 田中 宏和; 佐藤 友亮; 松村 到; 金倉 譲  日本癌学会総会記事  69回-  86  -86  2010/08
  • 非炎症状態の樹状細胞分化における白血病関連遺伝子異常の役割(Leukemia-related gene abnormalities affect steady-state dendritic cell differentiation)
    藤田 二郎; 水木 満佐央; 江副 幸子; 田中 宏和; 佐藤 友亮; 福島 健太郎; 徳永 正浩; 松村 到; 金倉 譲  日本癌学会総会記事  69回-  161  -161  2010/08
  • M. Tokunaga; S. Ezoe; H. Tanaka; Y. Satoh; I. Matsumura; Y. Kanakura  HAEMATOLOGICA-THE HEMATOLOGY JOURNAL  95-  50  -50  2010/06
  • 臍帯血CD34陽性細胞のex vivo増幅技術の開発と臨床応用
    田中 宏和; 伊藤 仁也; 前川 平; 中畑 龍俊; 金倉 譲  医工学治療  21-  (Suppl.)  111  -111  2009/04
  • 癌治療への再生医療の応用 Ex vivo増幅造血幹/前駆細胞の臍帯血移植への応用
    田中 宏和; 伊藤 仁也; 丸山 京子; 中畑 龍俊  再生医療  6-  (4)  385  -390  2007/11
  • FIP1L1/PDGFRaは造血幹細胞/前駆細胞の好酸球系への分化を誘導する(FIP1L1/PDGFRa imposes commitment towards eosinophic lineage on hematopoietic stem/progenitor cells)
    福島 健太郎; 松村 到; 江副 幸子; 佐藤 友亮; 安見 正人; 田中 宏和; 金倉 譲  日本癌学会総会記事  66回-  299  -299  2007/08
  • 細胞治療の基盤と臨床応用 増幅臍帯血を用いた移植
    田中 宏和; 伊藤 仁也; 中畑 龍俊  日本輸血細胞治療学会誌  53-  (2)  184  -184  2007/04
  • GSK3-β阻害剤が造血幹/前駆細胞の増殖、分化に及ぼす影響についての検討
    田中 宏和; 松村 到; 伊藤 仁也; 多田 典子; 中畑 龍俊; 金倉 譲  臨床血液  47-  (9)  1079  -1079  2006/09
  • Y Satoh; Matsumura, I; S Ezoe; H Tanaka; T Yokota; J Ishikawa; K Oritani; Y Kanakura  BLOOD  106-  (11)  494A  -494A  2005/11
  • AML1のC端欠失変異体が造血幹/前駆細胞に及ぼす影響についての解析
    佐藤 友亮; 松村 到; 田中 宏和; 江副 幸子; 金倉 譲  日本血液学会・日本臨床血液学会総会プログラム・抄録集  67回・47回-  886  -886  2005/09
  • AML1のC端欠失変異体が造血幹/前駆細胞に及ぼす影響についての解析
    佐藤 友亮; 松村 到; 田中 宏和; 江副 幸子; 金倉 譲  日本癌学会総会記事  64回-  157  -157  2005/09
  • 転写因子PBX1によるヒト臍帯血造血幹細胞の増殖,分化制御機構の解析
    田中 宏和; 伊藤 仁也; 多田 典子; 佐藤 友亮; 中畑 龍俊; 金倉 譲  炎症・再生  23-  (6)  443  -443  2003/11
  • 完全無血清培養系で増幅した臍帯血造血幹細胞の特徴
    初山 麻子; 伊藤 仁也; 田中 宏和; 中畑 龍俊  臨床血液  44-  (8)  729  -729  2003/08
  • A Kawasaki; Matsumura, I; H Tanaka; S Ezoe; T Machii; Y Kanakura  BLOOD  96-  (11)  684A  -684A  2000/11
  • H Tanaka; Matsumura, I; A Kawasaki; S Ezoe; Y Kanakura  BLOOD  96-  (11)  290A  -290A  2000/11
  • S Ezoe; Matsumura, I; H Tanaka; A Kawasaki; T Machii; T Enver; Y Kanakura  BLOOD  96-  (11)  285A  -285A  2000/11
  • S Ezoe; Matsumura, I; H Tanaka; A Kawasaki; T Machii; T Enver; K Kanakura  BLOOD  96-  (11)  680A  -680A  2000/11
  • A Kawasaki; Matsumura, I; R Fukunaga; H Tanaka; S Ezoe; T Machii; S Nagata; Y Kanakura  BLOOD  96-  (11)  165B  -165B  2000/11

Industrial Property Rights

Research Grants & Projects

  • 日本学術振興会：科学研究費助成事業
    Date (from‐to) : 2023/04 -2026/03 
    Author : 田中 宏和; 松村 到; 芹澤 憲太郎; 森田 泰慶
  • 日本学術振興会：科学研究費助成事業
    Date (from‐to) : 2022/04 -2025/03 
    Author : 松村 到; 田中 宏和; 口分田 貴裕; 森田 泰慶
  • 日本学術振興会：科学研究費助成事業 基盤研究(C)
    Date (from‐to) : 2020/04 -2023/03 
    Author : 田中 宏和; 松村 到; 頼 晋也; 森田 泰慶
     
    本研究では、多発性骨髄腫(MM)幹細胞を用いて、免疫チェックポイント分子の発現変化と発現調節機序を解析するとともに、同一患者由来の免疫担当細胞の特性を解析することで、MM患者の病態と抗腫瘍免疫との関連を包括的に明らかにすることを目的とする。昨年度はMM細胞集団CD38+138+45-19- (phenotypic MM cell, phMC）を幹細胞マーカーであるCD34の発現の有無によりCD34+, CD34- PhMCに分離し、それぞれにおける免疫チェックポイント分子の発現を網羅的に比較した。その結果CD274 (PDL1), CD155 (TIGIT), CD270 (TNFSFR14), GAL9等の抗腫瘍免疫の抑制分子の発現が、CD34-PhMCと比較してCD34+ PhMCにおいて有意に高いことを見出した。本年度は、これら分子が抗骨髄腫免疫に果たす機能について共培養系を用いて検討した。CD34+ phMC と同一症例から得た樹状細胞, pDC、細胞障害性T細胞, CTLとの共培養の系（Ref. Cancer Cell. 2009; 16: 309-23.）を用いた。各免疫チェックポイント分子の中和抗体を添加することによるCTL活性の変化を、CTLの増殖能、培養上清へのサイトカイン放出能等を評価することで、CTL 活性に及ぼす免疫チェックポイント分子の同定を試みた。その結果、症例ごとにMM 特異的 CD8+ CTL 活性を引き起こす中和抗体は異なり、症例ごとに免疫抑止に関わる分子は異なることが明らかになった。
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2018/04 -2021/03 
    Author : MATSUMUTA Itaru
     
    In this study, we analyzed immune evasion mechanisms of residual chronic myeloid leukemia stem cells (CML-LSCs) during the treatment with tyrosine kinase inhibitors (TKIs). Both expression of immune checkpoint molecule, PDL1 and activation of immunosuppressive enzyme, IDO1 were induced through the activation of CD120a/NF-κB signaling pathway in phenotypically defined CD34+38-120a+225+ cells, which we previously identified as CML-LSC. Furthermore, CML-LSCs suppressed cytotoxic T cell activity and induced a local recruitment of immunosuppressive populations such as regulatory T cells and myeloid-derived suppressor cells, leading to an immunosuppressive bone marrow milieu undergoing TKI therapy.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2016/04 -2019/03 
    Author : TANAKA Hirokazu; SERIZAWA kentaro
     
    We isolated myeloma initiating cells from phenotypically defined CD38+ CD 138+ CD 19- CD 45- multiple myeloma (MM) cells (PhMCs) from a set of 54 bone marrow MM patient samples. And we found PhMCs contains a minor CD34+ fraction that possess myeloma-propagating activities in vitro and in vivo, as well as resistance to anticancer drugs. The percent of CD34+ PhMCs was significantly higher in relapse/refractory than in newly diagnosed samples. Gene expression profiling revealed that CD34- PhMCs had a general myeloma cell signature, whereas CD34+ PhMCs exhibited a more immature pre-germinal center like signature. The presence of e cancer stem cells in MM was proposed for a few decades, however the identity of these cells remains controversial. The identification of these MM propagating cells provides a basis for better understanding the pathogenesis of MM and for designing novel therapeutic strategies aimed to eradicate total MM cells.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2015/04 -2018/03 
    Author : MATSUMURA Itaru
     
    We here show that pharmacologic inhibition of clathrin-dependent trafficking of mutated receptor tyrosine kinases (mtRTK such as FLT3-ITS and KIT D814V mutation) with chlorpromazine (CPZ) disrupts their cellular localization and inhibits their activities. CPZ suppressed the growth of primary AML cells with mtRTK, including CD34+38- AML stem cells in vitro. In mice transplanted with primary AML cells, administration of CPZ at a clinically relevant concentration inhibited the growth of AML cells with mtRTK while it showed a marginal effect on the growth of AML cells with wild-type RTK. Also, CPZ treatment eliminated AML stem cells at the periosteal region in the bone marrow of the recipient mice. These results demonstrate that the intracellular trafficking of mtRTKs would be a good therapeutic target and CPZ would be new therapeutic agent against AML with mtRTK.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2014/04 -2017/03 
    Author : SATOH YUSUKE; TANAKA HIROKAZU
     
    We generated hematological-lineage restricted SATB1 conditional knock out (cKO) mice. Analyzing the adult bone marrow (BM) in these mice, we observed a significant decrease in the number of HSCs as compared to those in their wild type (WT) littermates. SATB1 cKO mice-derived HSCs showed lower BM reconstitution ability than WT HSCs. Next, we generated SATB1 reporter mice, and examined the early differentiation of HSCs. We found that the HSC fraction of adult BM consists of SATB1－ and SATB1+ cells. In transplantation experiments, the SATB1+ HSCs produced more lymphocytic cells and fewer myeloid cells in the recipients. The membrane protein MS4A3 is negatively regulated by SATB1, and we found that MS4A3 expression was observed in primary acute myeloid leukemia cases. In addition , a MS4A3 antibody induced complement-dependent cell death in several human AML lines. These results suggest that MS4A3 may serve as a putative therapeutic target to treat myeloid malignancies.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2013/04 -2016/03 
    Author : TANAKA Hirokazu; MATSUMURA Itaru; HIRASE Chikara
     
    FLT3-ITD and KIT D816V mutation are frequently found in AML and associated with poor prognosis. In this study, we evaluated the anti-leukemic effects of an inhibitor of membrane trafficking, chlorpromazine (CPZ). Recent studies demonstrated that these oncogenic RTKs are mislocalized in the cytoplasm, where they transmit aberrant signals to downstream. CPZ disrupted the intracellular trafficking of RTK mutants, and significantly suppressed activities of RTK mutants and their downstream molecules. Consequently, CPZ inhibited the growth and survival of AML cells with mutant RTK in a dose-dependent manner. In xenotransplantation models, administration of CPZ significantly reduced engraftment of AML cells, and also showed the cytotoxic effect to AML stem cells, while displaying minimal toxicity to normal hematopoietic cells. These results suggest that CPZ would be a promising therapeutic drug to eradicate AML cells with an established safety profile.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2010 -2012 
    Author : SHIBAYAMA Hirohiko; KANAKURA Yuzuru; TANAKA Hirokazu
     
    The proliferation of B lymphocytes (B) from anamorsin (AM) transgenic (Tg) mice by LPS was impaired compared with WT B. The Western blotting analysis showed the phosphorylation of ERK1/2 and IkB were reduced. Furthermore, the expression of IL-1β mRNA was decreased in AM Tg B by DNA array compared with WT B. From these data, it was clarified that AM overexpression had negative effects on LPS-induced signal pathways of B.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research
    Date (from‐to) : 2010 -2011 
    Author : MATSUMURA Itaru; KANAKURA Yuzuru; MIZUKI Masao; ORITANI Kenji; SHIBAYAMA Hirohiko; ASHIDA Takashi; TATSUMI Yoichi; SHIMADA Takahiro; TANAKA Hirokazu
     
    In this study, we generated BCR-ABL transgenic mice using the tetraploid embryonic complementation method, in which we can turn on or off the BCR-ABL gene using the Tet-off system. In these mice, CML-like disease was induced about 1 month after the Tet-off, which was disappeared by Tet-on. The change of the methylation profile was observed two months after Tet-off, indicating that BCR-ABL secondary causes the abnormality in the methylation profile.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)
    Date (from‐to) : 2009 -2010 
    Author : TANAKA Hirokazu
     
    In this study, we conducted the analyses regarding how does excessive "free"iron affect the growth and differentiation of hematopoietic cells as well as the characteristic of hematopoietic stromal cells.In addition, we investigated the effects of iron overload on the proliferation of MDS clones and the pathological transformation of MDS. As a result, excessive iron impairs hematopoiesis through direct effects on hematopoietic cells and indirect effects mediated by stromal cells. Furthermore, iron overload may induce the selective proliferation of MDS clones during the deterioration of normal hematopoiesis and may be involved in the leukemic transformation. These results are significant to reveal the mechanism and treatment of various hematopoietic disorders in terms of iron-kinetics.
  • 日本学術振興会：科学研究費助成事業 若手研究(B)
    Date (from‐to) : 2006 -2007 
    Author : 田中 宏和
     
    転写因子NF-κBの個体発生における役割については未だ不明な点が多い.本研究では、ES細胞からの中胚葉系細胞への分化過程、及び造血細胞/血管内皮細胞の発生過程におけるNF-κBの機能について解析を行った. LIF非存在下にES細胞を分化誘導した場合、培養4.5日には血球、血管内皮に共通の前駆細胞を含むFlk-1陽性細胞が約30%出現したが、ES細胞にTet-off systemを用いてdominant negative NF-κB,IκBSRを誘導した場合、活性酸素種(ROS)依存的なapoptosisが誘導され、Flk-1の発現は強く抑制されていた.抗酸化剤処理によりapoptosisを回避した場合においてもFlk-1陽性細胞の出現は認められず、LIF除去によりFlk-1プロモーターがNF-κBにより活性化されていたことから、NF-κBはES細胞から中胚葉系細胞への分化過程においてROSを介したapoptosisを抑制すると同時に、機能分子であるFlk-1の発現を転写レベルで制御していると考えられた.次にテトラプロイド凝集胚法を用いてキメラマウスを作成し、原腸形成期以降にIκBSRを誘導した場合、E7.5胚においてIκBSRを誘導しなかった場合と同様に汎中胚葉マーカーの発現が認められたが、以後の造血及び脈管形成が障害され、Ell.5胚では肉眼的に貧血を呈し、血管網の形成が強く抑制されていた.さらにE10.5胚からAGM領域の細胞を採取し、IκBSRを誘導した場合の二次造血能について検討を行った結果、コロニー形成能が著明に障害され、ROS依存的なapoptosisが誘導された. 以上の結果から、NF-κBはFlk-1の他種々の遺伝子発現を介して中胚葉系細胞のapoptosisや分化を制御すること、さらにはマウス発生過程における造血及び脈管形成に重要な役割を担っていると推測された.
  • 日本学術振興会：科学研究費助成事業 若手研究(B)
    Date (from‐to) : 2003 -2004 
    Author : 田中 宏和
     
    本年度我々は、血液細胞の増殖、分化及び造血発生における活性酸素種ROSの役割について解析を行った。 IL-3依存性マウス白血病細胞株Ba/F3を用い、優勢阻害型のNF-κB(IκBSR)を細胞内に誘導出来る系を作成した。さらにこの系に各種サイトカインレセプターを導入することで、各々のサイトカイン依存性の亜株を樹立した。各種サイトカイン存在下IκBSRを誘導した場合、TPO,G-CSFによる増殖には影響されなかったが、低濃度でのIL-3,EPOによる増殖が有意に抑制された。一方サイトカイン除去後にIκBSRを誘導した場合、過剰なROSの蓄積を伴うapoptosisが認められた。さらにマウス骨髄より分離した造血幹、前駆細胞にIκBSRを導入した場合、至適サイトカイン存在下においても過剰なROSの蓄積を伴うapoptosisが認められた。抗酸化剤処理により、apoptosisが有意に減少することから、生体内での血液細胞の増殖、apoptosisにROSが重要な役割を担っていると推測された。 次に造血発生における活性酸素種ROSの役割について解析を行った。マウスES細胞をLIF非存在下OP-9ストローマ細胞と共培養すると4日目に血液、血管共通の前駆細胞が出現し、それ以降には至適サイトカイン存在下で、各種血球細胞が出現する(OP-9 system)。本systemにおいてIκBSRを誘導させた場合の各種血球細胞の出現に及ぼす影響を検討したところ、赤血球系、巨核球系、及び骨髄球系いずれの出現も有意に抑制され、多くの細胞にapoptosisが認められた。抗酸化剤処理により、成熟血球への分化誘導が改善することから、造血発生においてもROSが重要な役割を担っていると推測された。 以上の結果、生体内での血液細胞の増殖、分化及び造血発生において、ROSを介したapoptosisの制御が重要であること、さらにROSの産生、消去にはNF-κBが関与していることが示唆された。

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