AKT1 and acute myeloid leukemia: In hematologic malignancies, targeting Pim kinases in combination with standard treatment has proved useful in overcoming resistance in preclinical models, for example, combination with JAK2 inhibition in MPN65 and combination with cytarabine in AML.66 Pim-2 confers resistance in hematopoietic cells to rapamycin inhibition of mTOR.35, 67 Rationale for targeting the Pim and PI3K/AKT/mTOR pathways in combination is discussed below.