Cell type-specific apoptosis resistance in juvenile myelomonocytic leukemia

Juvenile myelomonocytic leukemia (JMML) is caused by constitutively activated RAS signaling. Activation of the RAS pathway in the JMML mouse model (MxCre;Ptpn11D61Y) affects apoptosis signaling by regulating BCL-2 family members through oncogenic and microenvironemtal signals, in a cell type-dependent manner. Apoptosis resistance mediated by overexpression of anti-apoptotic and downregulation of pro-apoptotic BCL-2 family members was observed in monocytes and granulocytes. To investigate gene expression changes in the JMML mouse model, RNA sequencing was performed in CD11b+ cells derived from BM and spleen and also from stem and progenotor LSK cells from BM, isolated from stage 3 (S3)MxCre;Ptpn11D61Y/+ mice. MxCre mice were used as controls.