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首页> 外文期刊>Journal of Clinical Oncology >CEBPA mutations in younger adults with acute myeloid leukemia and normal cytogenetics: prognostic relevance and analysis of cooperating mutations.
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CEBPA mutations in younger adults with acute myeloid leukemia and normal cytogenetics: prognostic relevance and analysis of cooperating mutations.

机译：患有急性髓细胞性白血病和正常细胞遗传学的年轻成年人中的CEBPA突变：预后相关性和协同突变分析。

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PURPOSE: To assess the prognostic relevance of mutations in the CEBPA gene encoding CCAAT/enhancer binding protein alpha (C/EBP alpha) 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/EBP alpha 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/EBP alpha 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.
机译：目的：在大量预期患有急性髓细胞白血病（AML）和正常细胞遗传学的年轻成年人中，评估编码CCAAT /增强子结合蛋白α（C / EBPα）的CEBPA基因突变的预后相关性。病人和方法：对236例16至60岁正常细胞遗传学的AML患者的诊断样本中的整个CEBPA编码区进行了测序，这些患者接受了AML研究小组Ulm连续两次方案的统一治疗，并且CEBPA突变状态与临床结果。结果：236例患者中有36例（15％）检出CEBPA突变。 236名患者中有21名（9％）的突变预计会导致C / EBPα功能丧失。 36例CEBPA突变的患者的缓解时间和总生存期（OS）明显更长（分别为P = .01和P = .05）。在多变量分析中，野生型CEBPA是影响缓解持续时间（危险比，2.85; P = .01）和OS（危险比，1.87; P = .04）的独立预后指标。对协作突变（激活的FLT3突变和MLL部分串联重复的两种类型）的分析表明，对于CEBPA突变的患者，FLT3突变对预后没有明显影响。此外，CEBPA突变的预计C / EBPα功能丧失的患者亚组与FLT3或MLL突变的患者之间无明显重叠，这表明CEBPA功能丧失的突变定义了正常的AML的独特生物学亚类。细胞遗传学。结论：突变CEBPA可预测具有良好细胞遗传学特征的AML患者的预后并可能改善其危险分层。

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