title: Presence of isocitrate dehydrogenase mutations may predict clinical response to hypomethylating agents in patients with acute myeloid leukemia.
abstract: Mutations in IDH1 and IDH2 occur in 15-20% of AML cases, resulting in the production of 2-hydroxyglutarate, which promotes aberrant hypermethylation of DNA in leukemic cells. Although these mutations have been shown to have prognostic implications for patients with AML, optimal treatment strategies have yet to be defined. We retrospectively identified forty-two patients with AML treated with DNA methyltransferase inhibitors (DNMTIs) decitabine (n = 36) or azacitidine (n = 6) and performed analysis of stored samples for the presence of IDH1 and IDH2 mutations. Of the forty-two samples analyzed, seven (16.7%) had IDH mutations. Thirteen patients (31%) achieved remission [(complete remission (CR)/complete remission with incomplete count recovery (CRi)/partial response (PR)] after treatment with a DNMTI, five of seven (71.4%) with IDH mutations and eight of thirty-five (22.9%) without IDH mutations (P = 0.01). When adjusted for age at diagnosis, sex, bone marrow blast percentage and cytogenetic, the odds of achieving response after administration of a DNMTI among patients with an IDH mutation was 14.2 when compared to patients without an IDH mutation (95%CI: 1.3-150.4). IDH1 and IDH2 mutations may predict a favorable response to DNMTI in patients with AML.
authors: School of Medicine, Department of Internal Medicine, University of Maryland Greenebaum Cancer Center, University of Maryland, Baltimore, Maryland.
authors: Ashkan
authors: A
authors: Emadi
authors: Rawan
authors: R
authors: Faramand
authors: Brandon
authors: B
authors: Carter-Cooper
authors: Seda
authors: S
authors: Tolu
authors: Laurie A
authors: LA
authors: Ford
authors: Rena G
authors: RG
authors: Lapidus
authors: Meir
authors: M
authors: Wetzler
authors: Eunice S
authors: ES
authors: Wang
authors: Arash
authors: A
authors: Etemadi
authors: Elizabeth A
authors: EA
authors: Griffiths
mesh_terms: D000367:Age Factors; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001374:Azacitidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors; D000077209:Decitabine; D005260:Female; D005838:Genotype; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D009154:Mutation; D016017:Odds Ratio; D011379:Prognosis; D012074:Remission Induction; D012189:Retrospective Studies; D012737:Sex Factors
chemical_list: D000964:Antimetabolites, Antineoplastic; D000077209:Decitabine; C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D015254:DNA Modification Methylases; D001374:Azacitidine