Prognostic impact of IDH2 mutations in cytogenetically normal acute myeloid leukemia.
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.
Thol
Felicitas
F
Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Carl-Neuberg Strasse 1, Hannover, Germany. thol.felicitas@mh-hannover.de
Damm
Frederik
F
Wagner
Katharina
K
Göhring
Gudrun
G
Schlegelberger
Brigitte
B
Hoelzer
Dieter
D
Lübbert
Michael
M
Heit
Wolfgang
W
Kanz
Lothar
L
Schlimok
Günter
G
Raghavachar
Aruna
A
Fiedler
Walter
W
Kirchner
Hartmut
H
Heil
Gerhard
G
Heuser
Michael
M
Krauter
Jürgen
J
Ganser
Arnold
A
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
C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase