title: IDH2 inhibition in AML: Finally progress?
abstract: Isocitrate dehydrogenase (IDH) catalyzes the conversion of isocitrate to alpha ketoglutarate. IDH occurs in three isoforms, IDH1, located in the cytoplasm, IDH2 located in the mitochondria, and IDH3, which functions as part of the TCA cycle. Mutations in the active site of IDH1 at position R132 and an analogous mutation in the IDH2 gene at position R172 have been discovered. Notably, many cases of acute myeloid leukemia (AML) have mutations in R172 and R140. The impact of these mutations and early results of inhibiting mutant IDH2 with the reversible inhibitor AG-221 are discussed in this review.
authors.affiliation: Leukemia Service, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, 1275 York Avenue, New York, NY 10065, USA. Electronic address: steine@mskcc.org.
authors.forename: Eytan M
authors.initials: EM
authors.lastname: Stein
mesh_terms: D000631:Aminopyridines / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002135:Calcium-Binding Proteins; D017321:Clinical Trials, Phase I as Topic; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D015870:Gene Expression; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D012008:Recurrence; D012074:Remission Induction; D016019:Survival Analysis; D014227:Triazines / Q000627:therapeutic use*
chemical_list: D000631:Aminopyridines; D000970:Antineoplastic Agents; D002135:Calcium-Binding Proteins; D004791:Enzyme Inhibitors; C104144:NELL1 protein, human; D009419:Nerve Tissue Proteins; D014227:Triazines; C000605269:enasidenib; C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human
keywords: 2-HG; Acute myeloid leukemia; Isocitrate dehydrogenase