This is consistent with preclinical studies in which IDH1/2 mutant AML, via the oncometabolite (R)-2-HG, inhibits the activity of cytochrome c oxidase (COX) in the mitochondrial electron transport chain (ETC), which in turn, lowered the mitochondrial threshold to trigger apoptosis upon BCL-2 inhibition [61]. Here, IDH1 is linked to acute myeloid leukemia.