检验医学 ›› 2017, Vol. 32 ›› Issue (9): 784-790.DOI: 10.3969/j.issn.1673-8640.2017.09.009

• 临床应用研究·论著 • 上一篇    下一篇

DNMT3AFLT3-ITD突变与AML患者不良预后的相关性

马娟1, 沈立松1   

  1. 1.上海交通大学医学院附属新华医院检验科,上海 200092
    2. Department of Pathology and Laboratory Medicine,Oregon Health and Science University,Portland,Oregon 97239
  • 收稿日期:2017-06-23 出版日期:2017-09-30 发布日期:2017-09-30
  • 作者简介:null

    作者简介:马 娟,女,1993年生,硕士,主治医师,主要从事血液系统疾病的相关机制和实验室诊断研究。

Correlation of the poor prognosis of acute myeloid leukemia with FLT3-ITD and DNMT3A mutations

MA Juan1, SHEN Lisong1, Jennifer Dunlap2, FAN Guang2   

  1. 1. Department of Clinical Laboratory,Xinhua Hospital,Shanghai Jiaotong University School of Medicine,Shanghai 200092,China
    2. Department of Pathology and Laboratory Medicine,Oregon Health and Science University, Portland 97239,Oregon,USA
  • Received:2017-06-23 Online:2017-09-30 Published:2017-09-30

摘要:

目的探讨FLT3-ITDDNMT3A突变对细胞遗传学中等风险的急性髓系白血病(AML)患者预后评估的价值。方法 选取2010—2016年美国俄勒冈州健康与科学大学附属医院收治的AML初诊患者132例,根据细胞遗传学分析结果将患者分为预后良好细胞遗传学组(简称预后良好组)24例、中等风险细胞遗传学组(简称中等风险组)79例、不良风险细胞遗传学组(简称不良风险组)27例,另有细胞遗传学信息不详2例。使用下一代测序(NGS)技术检测与血液系统肿瘤发病相关的42个基因突变。结果 132例AML患者中有120例(91%)至少发生1个基因突变,多基因(≥2)突变占61%。Kaplan-Meier生存曲线显示,在中等风险组中,FLT3-ITD突变阳性组的总体生存期与FLT3-ITD突变阴性组比较,差异有统计学意义(P<0.001)。进一步分析发现,FLT3-ITD突变阳性+DNMT3A突变组的中位生存期明显短于FLT3-ITD突变阴性组(P<0.001),FLT3-ITD突变阳性+DNMT3A野生型组的中位生存期与FLT3-ITD突变阴性组比较,差异无统计学意义(P>0.05)。FLT3-ITD突变阳性+DNMT3A突变组的总生存期明显短于FLT3-ITD突变阴性组(P<0.001)和FLT3-ITD突变阳性+DNMT3A野生型组(P=0.003)。结论 在细胞遗传学中等风险的AML患者中,如果同时存在FLT3-ITDDNMT3A突变,提示预后不良。检测FLT3-ITDDNMT3A突变状态有助于对AML进行预后评估。

关键词: FLT3-ITD基因, DNMT3A基因, 突变, 急性髓系白血病, 预后因素

Abstract:

Objective To investigate the roles of FLT3-ITD and DNMT3A mutations in the prognosis of acute myeloid leukemia(AML) patients in intermediate-risk-cytogenetic-group. Methods A total of 132 de novo AML patients were enrolled from the Affiliated Hospital of Oregon Health and Science University from 2010 to 2016,and they were classified into favorable-risk-cytogenetic-group(24 cases),intermediate-risk-cytogenetic-group(79 cases) and adverse-risk-cytogenetic-group(27 cases). There were 2 cases with unknown cytogenetic information. Totally,42 genes being relevant to hematopoietic malignancies were determined by next generation sequencing(NGS). Results There were 91%(120/132) of AML cases with at least one mutation,and the pattern of co-mutations(≥2) accounted for 61%. Kaplan-Meier analysis demonstrated that the overall survival in FLT3-ITD mutation positive group for intermediate-risk-cytogenetic-group had statistical significance with that in FLT3-ITD mutation negative group(P<0.001). When DNMT3A was co-mutated,FLT3-ITD mutation positive group had a shorter overall survival compared to FLT3-ITD mutation negative group(P<0.001). In the present of DNMT3A wildtype,there was no statistical significance for overall survival between FLT3-ITD mutation positive and FLT3-ITD mutation negative groups(P>0.05). FLT3-ITD mutation positive with DNMT3A mutation group had a shorter overall survival compared to FLT3-ITD mutation negative group(P<0.001) and FLT3-ITD mutation positive with DNMT3A wildtype group(P=0.003). Conclusions In intermediate-risk-cytogenetic-group,the co-mutations of FLT3-ITD and DNMT3A have an adverse prognosis. The determinations of FLT3-ITDand DNMT3A mutations may be needed to refine prognostication and guide clinical management in AML.

Key words: FLT3-ITD gene, DNMT3A gene, Mutation, Acute myeloid leukemia, Prognostic factor

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