Gene mutation patterns and their prognostic impact in a cohort of 1185 patients with acute myeloid leukemia
Gene mutation patterns and their prognostic impact in a cohort of 1185 patients with acute myeloid leukemia
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1185 名急性髓系白血病患者的基因突变模式及其预后影响
DOI：
10.1182/blood-2011-03-343988
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发表时间：
2011-11-17
期刊：
影响因子：
20.3
通讯作者：
Chen, Sai-Juan
中科院分区：
文献类型：
--
作者：
Shen, Yang;Zhu, Yong-Mei;Chen, Sai-Juan
为了评估基因突变对急性髓系白血病(AML)患者预后的价值，我们检测了1185例AML患者由于染色体易位和基因突变引起的AML1(CBFα)-ETO、CBFβ-MYH11、PML-RARα和MLL重排等融合产物的基因状态，以及FLT3、C-KIT、N-RAS、NPM1、CEBPA、WT1、ASXL1、DNMT3A、MLL、IDH1、IDH2和TET2基因突变。临床分析主要集中在除11q23外无可识别核型异常的605例患者中。在这605例患者中，452例(74.7%)被发现至少有1个突变，并研究了基因突变与临床结局的关系。我们揭示了NPM1、DNMT3A、Flt3、IDH1、IDH2、CEBPA和TET2突变之间的关联模式。多变量分析发现，DNMT3A和MLL突变是预测总体生存率(OS)和无事件生存率(EFS)的独立因素，而CEBPA双等位基因突变或NPM1突变(没有DNMT3A突变)在整个组和60岁以下的年轻患者中都具有更好的OS和EFS。分子标记的使用使我们能够将605名患者细分为具有潜在临床相关性的不同预后组。(血。2011；118(20)：5593-5603)
To evaluate the prognostic value of genetic mutations for acute myeloid leukemia (AML) patients, we examined the gene status for both fusion products such as AML1 (CBF alpha)-ETO, CBF beta-MYH11, PML-RAR alpha, and MLL rearrangement as a result of chromosomal translocations and mutations in genes including FLT3, C-KIT, N-RAS, NPM1, CEBPA, WT1, ASXL1, DNMT3A, MLL, IDH1, IDH2, and TET2 in 1185 AML patients. Clinical analysis was mainly carried out among 605 cases without recognizable karyotype abnormalities except for 11q23. Of these 605 patients, 452 (74.7%) were found to have at least 1 mutation, and the relationship of gene mutations with clinical outcome was investigated. We revealed a correlation pattern among NPM1, DNMT3A, FLT3, IDH1, IDH2, CEBPA, and TET2 mutations. Multivariate analysis identified DNMT3A and MLL mutations as independent factors predicting inferior overall survival (OS) and event-free survival (EFS), whereas biallelic CEBPA mutations or NPM1 mutations without DNMT3A mutations conferred a better OS and EFS in both the whole group and among younger patients < 60 years of age. The use of molecular markers allowed us to subdivide the series of 605 patients into distinct prognostic groups with potential clinical relevance. (Blood. 2011;118(20):5593-5603)