In this study, we used in vitro screening to identify the efficacy of a novel drug combination, pan-PIM inhibitor AZD1208 and dual-mTORC1/2 inhibitor AZD2014, and demonstrated that the combination of AZD2014 and AZD1208 synergistically inhibited growth of AML regardless of FLT3 mutation status through impaired polysome assembly and induction of apoptosis. Here, PIM1 is linked to acute myeloid leukemia.