Co-targeting of BCL-2 and MCL-1 overcomes BAX deficiency-mediated resistance of TP53-mutant AML and AML stem/progenitor cells to individual BH3 mimetics in vitro and in xenografts comprising both TP53-WT and -mutant Molm13 cells in vivo. The gene discussed is BCL2; the disease is acute myeloid leukemia.