IDH1 and acute myeloid leukemia: This is different from acute myeloid leukemia in which Bcl-2 inhibition was identified as synthetic lethal to elevated levels of the oncometabolite D-2HG caused by mutations in IDH1 or IDH2. The authors propose a model in which D-2HG inhibits the activity of cytochrome c oxidase (COX) in the mitochondrial electron transport chain, which lowers the threshold to trigger apoptosis after Bcl-2 inhibition12.