Reconstitution of p53 tumor-suppressor activity, through treatment with the MDM2 antagonist idasanutlin, and induction of mitochondrial apoptosis, through specific Bcl-2 inhibition with the BH3 mimetic venetoclax, led to anti-tumor effects in both in vitro and in vivo human xenograft models of AML. Here, BCL2 is linked to acute myeloid leukemia.