Acquired expression of CblQ367P induces sustained proliferation of myelomonocytes, multilineage dysplasia, and splenomegaly resembling CMML. Combined inhibition of PI3K and JAK2 efficiently suppressed the growth of CblQ367P-induced CMML cells.

Fbxl10 is a bona fide oncogene in vivo. Fbxl10 overexpression in HSCs induces mitochondrial metabolic activation and enhanced expression of Nsg2.

Despite their self-sufficient ability to generate capped mRNAs from cytosolic DNA genomes, poxviruses must commandeer the critical eukaryotic translation initiation factor 4F (eIF4F) to recruit ribosomes. While eIF4F integrates signals to control translation, precisely how poxviruses manipulate the multisubunit eIF4F, composed of the cap-binding eIF4E and the RNA helicase eIF4A assembled onto an eIF4G platform, remains obscure. Here, we establish that the poxvirus infection of normal, primary human cells destroys the translational repressor eIF4E binding protein (4E-BP) and promotes eIF4E assembly into an active e1F4F complex bound to the cellular polyadenylate-binding protein (PABP). Stimulation of the eIF4G-associated kinase Mnk1 promotes eIF4E phosphorylation and enhances viral replication and protein synthesis. Remarkably, these eIF4F architectural alterations are accompanied by the concentration of eIF4E and e1F4G within cytosolic viral replication compartments surrounded by PABP. This demonstrates that poxvirus infection redistributes, assembles, and modifies core and associated components of e1F4F and concentrates them within discrete subcellular compartments. Furthermore, it suggests that the subcellular distribution of e1F4F components may potentiate the complex assembly.