Therapeutic targeting of the anti-apoptotic protein B-cell lymphoma-2 (BCL-2) with venetoclax in combination with hypomethylating agents or low-dose cytarabine induces high rates of complete remission in newly diagnosed elderly patients and those with R/R AML.(7–10) However, failure of venetoclax is associated with especially poor outcomes with a median OS of 2.4 months.(11) Resistance to venetoclax commonly arises as a result of either overexpression of other antiapoptotic BCL2 family members such as MCL1 and BCL-XL or inactivation of P53. This evidence concerns the gene MCL1 and acute myeloid leukemia.