Several lines of evidence demonstrated that BIM is an essential regulator of leukopoiesis and plays a central role in Sorafenib-induced AML cell death.36,37 Expression of PUMA is also upregulated by FLT3 TKIs.38 The interaction between PUMA and BCL-2 or MCL-1 is enhanced when FLT3/ITD cells are treated with Sorafenib plus Clofarabine, Fludarabine, and Busulfan. This evidence concerns the gene BCL2 and acute myeloid leukemia.