Thus, IDH1/IDH2 mutations play a double role in leukemogenesis: first, mutants induce alterations in the pattern of histone modifications and aberrant DNA methylation, with consequent accumulation of epigenetic aberrancies, associated with reduced TET2 activity (26); second, mutants can rewire metabolism of AML blasts (25), with sustained inhibition of the activity of cytochrome c oxidase (COX) in the mitochondrial electron transport chain (20) and the glutamine addiction of AML cells for survival (32). The gene discussed is IDH1; the disease is acute myeloid leukemia.