title: Prognostic impact of IDH2 mutations in cytogenetically normal acute myeloid leukemia.
abstract: Mutations in the nicotinamide adenine dinucleotide phosphate(+)-dependent isocitrate dehydrogenase gene 2 (IDH2) have recently been found in patients with acute myeloid leukemia (AML) as well as in patients with leukemic transformation of myeloproliferative neoplasms. We analyzed 272 adult patients with cytogenetically normal AML (CN-AML) for the presence of IDH2 mutations in codons R140 and R172. IDH2 mutations of amino acid 140 or 172 could be identified in 12.1% of CN-AML patients, with the majority of mutations (90%) occurring at position R140. The incidence of IDH2 mutations in AML patients with aberrant karyotypes (n = 130) was significantly lower (3.8%, P = .006). IDH2 mutations were mutually exclusive with mutations in IDH1. IDH2 mutation status alone or in combination with IDH1 mutations had no impact on response to therapy, overall survival, and relapse-free survival in patients with CN-AML. In conclusion, IDH2 mutations are frequently found in CN-AML, but in our analysis these mutations did not influence treatment outcome. This study was registered at www.clinicaltrials.gov as #NCT00209833.
authors.affiliation: Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Carl-Neuberg Strasse 1, Hannover, Germany. thol.felicitas@mh-hannover.de
authors.forename: Felicitas
authors.initials: F
authors.lastname: Thol
authors.forename: Frederik
authors.initials: F
authors.lastname: Damm
authors.forename: Katharina
authors.initials: K
authors.lastname: Wagner
authors.forename: Gudrun
authors.initials: G
authors.lastname: Göhring
authors.forename: Brigitte
authors.initials: B
authors.lastname: Schlegelberger
authors.forename: Dieter
authors.initials: D
authors.lastname: Hoelzer
authors.forename: Michael
authors.initials: M
authors.lastname: Lübbert
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Heit
authors.forename: Lothar
authors.initials: L
authors.lastname: Kanz
authors.forename: Günter
authors.initials: G
authors.lastname: Schlimok
authors.forename: Aruna
authors.initials: A
authors.lastname: Raghavachar
authors.forename: Walter
authors.initials: W
authors.lastname: Fiedler
authors.forename: Hartmut
authors.initials: H
authors.lastname: Kirchner
authors.forename: Gerhard
authors.initials: G
authors.lastname: Heil
authors.forename: Michael
authors.initials: M
authors.lastname: Heuser
authors.forename: Jürgen
authors.initials: J
authors.lastname: Krauter
authors.forename: Arnold
authors.initials: A
authors.lastname: Ganser
mesh_terms: D000328:Adult; D002986:Clinical Trials as Topic; D020732:Cytogenetic Analysis; D004252:DNA Mutational Analysis; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics* / Q000502:physiology; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D015337:Multicenter Studies as Topic; D009154:Mutation / Q000502:physiology; D011379:Prognosis; D012008:Recurrence; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase