IDH2 and acute myeloid leukemia: In AML patients, IDH1/IDH2 gene mutations are heterozygous missense mutations involving a single arginine (R) residue in the enzyme active site (9), R132 in IDH1 and R140 or R172 in IDH2, restructuring the enzyme and leading to a reduced affinity of the mutant enzymes for isocitrate while increased affinity for α-ketoglutarate (αKG) and nicotinamide adenine dinucleotide phosphate (NADPH) with production of R-2HG (17), as extensively reviewed elsewhere (18).