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

被引:160
作者
Boissel, Nicolas
Nibourel, Olivier
Renneville, Aline
Gardin, Claude
Reman, Oumedaly
Contentin, Nathalie
Bordessoule, Dominique
Pautas, Cecile
de Revel, Thierry
Quesnel, Bruno
Huchette, Pascal
Philippe, Nathalie
Geffroy, Sandrine
Terre, Christine
Thomas, Xavier
Castaigne, Sylvie
Dombret, Herve
Preudhomme, Claude
机构
[1] Univ Paris 07, Paris, France
[2] Hop St Louis, AP HP, Paris, France
[3] CHU Lille, Hematol Lab, F-59037 Lille, France
[4] INSERM, U837, F-59045 Lille, France
[5] Univ Lille Nord France, Lille, France
[6] Inst Rech Canc Lille, Lille, France
[7] Avicenne Hosp, APHP, Bobigny, France
[8] Clemenceau Hosp, Caen, France
[9] Ctr Henri Becquerel, F-76038 Rouen, France
[10] Dupuytren Hosp, Limoges, France
[11] Hop Henri Mondor, APHP, F-94010 Creteil, France
[12] Hop Armees, Clamart, France
[13] Versailles Hosp, Lab Cytogenet, Le Chesnay, France
[14] Hop Edouard Herriot, Lyon, France
关键词
GENE-MUTATIONS; CYTOGENETIC ABNORMALITIES; CEBPA MUTATIONS; IDH2; MUTATIONS; AML; EXPRESSION; HYPOXIA; ADULTS; NPM1; AGE;
D O I
10.1200/JCO.2010.28.2285
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose 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. Patients and Methods 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. Results 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. Conclusion 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. J Clin Oncol 28: 3717-3723. (C) 2010 by American Society of Clinical Oncology
引用
收藏
页码:3717 / 3723
页数:7
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