title: Type and location of isocitrate dehydrogenase mutations influence clinical characteristics and disease outcome of acute myeloid leukemia.
abstract: Mutations of isocitrate dehydrogenase 1 and 2 (IDH1/2) are genetic alterations in acute myeloid leukemia (AML). The aim of our study was to investigate the frequency and prognostic effect of IDH1/2 mutations together followed by an individual analysis of each substitution in a Hungarian cohort consisting of 376 patients with AML. IDH1(mut) and IDH2(mut) were mutually exclusive, detected in 8.5% and 7.5% of cases, respectively. IDH1/2(mut) was associated with: older age (p = 0.001), higher average platelet count (p = 0.001), intermediate karyotype (p < 0.0001), NPM1(mut) (p = 0.022) and lower mRNA expression level of ABCG2 gene (p = 0.006). Overall survival (OS), remission and relapse rates were not different in IDH1(mut) or IDH2(mut) vs. IDH(neg). IDH1(mut) and IDH2(mut) were associated differently with NPM1(mut); co-occurrence was observed in 14.3% of IDH1 R132C vs. 70% of R132H carriers (p = 0.02) and in 47.4% of IDH2 R140Q vs. 0% of R172K carriers (p = 0.02). IDH1 R132H negatively influenced OS compared to IDH(neg) (p = 0.02) or R132C (p = 0.019). Particular amino acid changes affecting the same IDH1 codon influence the clinical characteristics and treatment outcome in AML.
authors.affiliation: Laboratory of Molecular Diagnostics, Hungarian National Blood Transfusion Service, Budapest, Hungary. m.koszarska@yahoo.pl
authors.forename: Magdalena
authors.initials: M
authors.lastname: Koszarska
authors.forename: Andras
authors.initials: A
authors.lastname: Bors
authors.forename: Angela
authors.initials: A
authors.lastname: Feczko
authors.forename: Nora
authors.initials: N
authors.lastname: Meggyesi
authors.forename: Arpad
authors.initials: A
authors.lastname: Batai
authors.forename: Judit
authors.initials: J
authors.lastname: Csomor
authors.forename: Emma
authors.initials: E
authors.lastname: Adam
authors.forename: Andras
authors.initials: A
authors.lastname: Kozma
authors.forename: Tamas I
authors.initials: TI
authors.lastname: Orban
authors.forename: Nora
authors.initials: N
authors.lastname: Lovas
authors.forename: Andrea
authors.initials: A
authors.lastname: Sipos
authors.forename: Eva
authors.initials: E
authors.lastname: Karaszi
authors.forename: Janos
authors.initials: J
authors.lastname: Dolgos
authors.forename: Sandor
authors.initials: S
authors.lastname: Fekete
authors.forename: Judit
authors.initials: J
authors.lastname: Reichardt
authors.forename: Eniko
authors.initials: E
authors.lastname: Lehoczky
authors.forename: Tamas
authors.initials: T
authors.lastname: Masszi
authors.forename: Attila
authors.initials: A
authors.lastname: Tordai
authors.forename: Hajnalka
authors.initials: H
authors.lastname: Andrikovics
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000090243:Nucleophosmin; D011379:Prognosis; D012008:Recurrence; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C000716967:NPM1 protein, human; D000090243:Nucleophosmin; C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human