CEBPA mutations in younger adults with acute myeloid leukemia and normal cytogenetics:: Prognostic relevance and analysis of cooperating mutations
CEBPA mutations in younger adults with acute myeloid leukemia and normal cytogenetics:: Prognostic relevance and analysis of cooperating mutations
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DOI：
10.1200/jco.2004.06.060
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发表时间：
2004-02-15
影响因子：
45.3
通讯作者：
Döhner, K
中科院分区：
文献类型：
--
作者：
Fröhling, S;Schlenk, RE;Döhner, K
目的评估编码CCAAT/增强子结合蛋白α的CEBPA基因突变与预后的关系（C/EBPalpha）在年轻成人急性髓性白血病（AML）的大型前瞻性系列研究中和正常细胞遗传学。患者和方法对来自236名16至60岁细胞遗传学正常的AML患者的诊断样本中的整个CEBPA编码区进行测序，这些患者接受了两次统一治疗AML研究组乌尔姆的连续方案，CEBPA突变状态与临床结局相关。236例患者中有21例（9%）发生了预测会导致C/EBPalpha功能丧失的突变。36例CEBPA突变患者的缓解期和总生存期（OS）显著延长（分别为P = 0.01和P = 0.05）。在多变量分析中，野生型CEBPA是影响缓解持续时间（风险比，2.85; P = 0.01）和OS（风险比，1.87; P = 0.04）的独立预后指标。对协同突变（两种类型的激活FLT 3突变和MLL部分串联重复）的分析表明，FLT 3突变对CEBPA突变患者的预后没有显著影响。此外，CEBPA突变的C/EBPalpha功能缺失患者亚组与FLT 3或MLL突变的患者亚组之间无明显重叠，提示CEBPA功能缺失突变定义了一个独特的AML生物学亚类，细胞遗传学正常。结论CEBPA突变预测预后良好，可能改善细胞遗传学正常的AML患者的危险分层。(C)2004年，美国临床肿瘤学会。
Purpose To assess the prognostic relevance of mutations in the CEBPA gene encoding CCAAT/enhancer binding protein alpha (C/EBPalpha) in a large prospective series of younger adults with acute myeloid leukemia (AML) and normal cytogenetics.Patients and Methods The entire CEBPA coding region was sequenced in diagnostic samples from 236 AML patients 16 to 60 years of age with normal cytogenetics who were uniformly treated on two consecutive protocols of the AML Study Group Ulm, and CEBPA mutation status was correlated with clinical outcome.Results CEBPA mutations were detected in 36 (15%) of 236 patients. Twenty-one (9%) of 236 patients had mutations predicted to result in loss of C/EBPalpha function. Remission duration and overall survival (OS) were significantly longer for the 36 patients with CEBPA mutations (P = .01 and P = .05, respectively). On multivariate analysis, wild-type CEBPA was an independent prognostic marker affecting remission duration (hazard ratio, 2.85; P = .01) and OS (hazard ratio, 1.87; P = .04). Analysis of cooperating mutations (both types of activating FLT3 mutations and MLL partial tandem duplications) showed that FLT3 mutations had no significant prognostic influence in patients with CEBPA mutations. Furthermore, there was no significant overlap between the subgroup of patients with CEBPA mutation with predicted loss of C/EBPalpha function and patients with FLT3 or MLL mutations, suggesting that CEBPA loss-of-function mutations define a distinct biologic subclass of AML with normal cytogenetics.Conclusion Mutant CEBPA predicts favorable prognosis and may improve risk stratification in AML patients with normal cytogenetics. (C) 2004 by American Society of Clinical Oncology.