Prognostic Impact of Isocitrate Dehydrogenase Enzyme Isoforms 1 and 2 Mutations in Acute Myeloid Leukemia: A Study by the Acute Leukemia French Association Group

异柠檬酸脱氢酶 髓系白血病 医学 IDH2型 内科学 IDH1 Fms样酪氨酸激酶3 肿瘤科 白血病 基因型 队列 净现值1 突变 基因 遗传学 生物 核型 生物化学 染色体
作者
Nicolas Boissel,Olivier Nibourel,Aline Renneville,Claude Gardin,Oumédaly Reman,Nathalie Contentin,Dominique Bordessoule,Cécile Pautas,Thierry de Revel,Bruno Quesnel,Pascal Huchette,N Philippe,Sandrine Geffroy,Christine Terré,Xavier Thomas,Sylvie Castaigné,Hervé Dombret,Claude Preudhomme
出处
期刊:Journal of Clinical Oncology [Lippincott Williams & Wilkins]
卷期号:28 (23): 3717-3723 被引量:215
标识
DOI:10.1200/jco.2010.28.2285
摘要

Recently, whole-genome sequencing in acute myeloid leukemia (AML) identified recurrent isocitrate dehydrogenase enzyme isoform (IDH1) mutations (IDH1m), previously reported to be involved in gliomas as well as IDH2 mutations (IDH2m). The prognosis of both IDH1m and IDH2m in AML remains unclear.The prevalence and the prognostic impact of R132 IDH1 and R172 IDH2 mutations were evaluated in a cohort of 520 adults with AML homogeneously treated in the French Acute Leukemia French Association (ALFA) -9801 and -9802 trials.The prevalence of IDH1m and IDH2m was 9.6% and 3.0%, respectively, mostly associated with normal cytogenetics (CN). In patients with CN-AML, IDH1m were associated with NPM1m (P = .008), but exclusive of CEBPAm (P = .03). In contrary, no other mutations were detected in IDH2m patients. In CN-AML patients, IDH1m were found in 19% of favorable genotype ([NPM1m or CEBPAm] without fms-related tyrosine kinase 3 [FLT3] internal tandem duplication [ITD]) and were associated with a higher risk of relapse (RR) and a shorter overall survival (OS). Favorable genotype in CN-AML could thus be defined by the association of NPM1m or CEBPAm with neither FLT3-ITD nor IDH1m. In IDH2m CN-AML patients, we observed a higher risk of induction failure, a higher RR and a shorter OS. In multivariate analysis, age, WBC count, the four-gene favorable genotype and IDH2m were independently associated with a higher RR and a shorter OS.Contrarily to what is reported in gliomas, IDH1m and IDH2m in AML are associated with a poor prognosis. Screening of IDH1m could help to identify high-risk patients within the subset of CN-AML with a favorable genotype.
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