Targeting mitochondrial B-cell lymphoma 2 (Bcl-2) has shown promise as an LSC-directed therapy in AML and the Bcl-2 inhibitor venetoclax is the only LSC-directed therapy currently in clinical use.113, 114, 115 Multiple mechanisms of action have been proposed for how venetoclax targets LSCs downstream of Bcl-2 inhibition, including depletion of amino acids, suppression of oxidative phosphorylation and disruption of energy metabolism.32 The gene discussed is BCL2; the disease is acute myeloid leukemia.