文章：

DNMT3A、U2AF1和EZH2突变可识别CR1后预后不良的急性髓系白血病中危患者

Mutations in DNMT3A, U2AF1, and EZH2 identify intermediate-risk acute myeloid leukemia patients with poor outcome after CR1

原文发布日期：2018-01-10

DOI: 10.1038/s41408-017-0040-9

类型: Article

开放获取: 是

英文摘要：

Intermediate-risk acute myeloid leukemia (IR-AML) is a clinically heterogeneous disease, for which optimal post-remission therapy is debated. The utility of next-generation sequencing information in decision making for IR-AML has yet to be elucidated. We retrospectively studied 100 IR-AML patients, defined by European Leukemia Net classification, who had mutational information at diagnosis, received intensive chemotherapy and achieved complete remission (CR) at Cleveland Clinic (CC). The Cancer Genome Atlas (TCGA) data were used for validation. In the CC cohort, median age was 58.5 years, 64% had normal cytogenetics, and 31% required >1 induction cycles to achieve CR1. In univariable analysis, patients carrying mutations in DNMT3A, U2AF1, and EZH2 had worse overall and relapse-free survival. After adjusting for other variables, the presence of these mutations maintained an independent effect on survival in both CC and TCGA cohorts. Patients who did not have the mutations and underwent hematopoietic cell transplant (HCT) had the best outcomes. HCT improved outcomes for patients who had these mutations. RUNX1 or ASXL1 mutations did not predict survival, and performance of HCT did not confer a significant survival benefit. Our results provide evidence of clinical utility in considering mutation screening to stratify IR-AML patients after CR1 to guide therapeutic decisions.

摘要翻译： 

中危急性髓系白血病（IR-AML）是一种临床异质性疾病，其最佳缓解后治疗方案尚存争议。新一代测序技术在中危急性髓系白血病治疗决策中的应用价值仍有待阐明。我们回顾性研究了克利夫兰医学中心100例经欧洲白血病网络分类定义的中危急性髓系白血病患者，这些患者在诊断时具有突变信息、接受强化疗并达到完全缓解。研究采用癌症基因组图谱数据进行验证。在克利夫兰队列中，患者中位年龄58.5岁，64%具有正常核型，31%需要超过1个诱导周期才能达到首次完全缓解。单变量分析显示，携带DNMT3A、U2AF1和EZH2基因突变的患者总生存期和无复发生存期更差。经其他变量调整后，这些突变在克利夫兰和癌症基因组图谱队列中均保持独立的生存影响。未携带这些突变且接受造血细胞移植的患者预后最佳。对于携带这些突变的患者，造血细胞移植可改善临床结局。RUNX1或ASXL1突变不能预测生存情况，进行造血细胞移植也未带来显著生存获益。我们的研究结果证实，在首次完全缓解后通过突变筛查对中危急性髓系白血病患者进行分层具有临床实用价值，可为治疗决策提供指导。

原文链接：

Mutations in DNMT3A, U2AF1, and EZH2 identify intermediate-risk acute myeloid leukemia patients with poor outcome after CR1