Using the model hematopoietic 32Dcl3 cell line expressing FLT3-ITD (32D/ITD) or FLT3-TKD (32D/TKD) and the FLT3-ITD-positive AML cell line MV4-11, we demonstrate that the pan-Pim kinase inhibitor AZD1208 or PIM447 downregulated the mTORC1/Mcl-1 pathway cooperatively with the PI3K/Akt pathway inhibitors in FLT3-ITD-expressing cells and abrogated the resistance of these cells to the PI3K/Akt inhibitors to induce apoptosis, while the resistance was conferred on FLT3-TKD-expressing cells by overexpression of Pim-1. Here, MCL1 is linked to acute myeloid leukemia.