When IL-2-activated primary NK cells were combined with BH3 mimetics that matched or mismatched the BH3 profiling–defined anti-apoptotic dominant dependencies of a panel of tumor cell lines, only the matched combinations yielded significant synergy (e.g., BCL2 blockade in BCL2-addicted acute-myeloid leukemia or MCL-1 blockade in MCL-1-dependent cervical carcinoma cells). The gene discussed is MCL1; the disease is acute myeloid leukemia.