DNMT3A、FLT3-ITD突变与AML患者不良预后的相关性  

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

作　　者：马娟[1] 沈立松[1] Jennifer Dunlap Fan Guang MA Juan;SHEN Lisong;Jennifer Dunlap;FAN Guang(Department of Clinical Laboratory,Xinhua Hospital,Shanghai Jiaotong University School of Medicine,Shanghai 200092,China;Department of Pathology and Laboratory Medicine,Oregon Health and Science University, Portland 97239,Oregon,USA)

机构地区：[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

出　　处：《检验医学》2017年第9期784-790,共7页Laboratory Medicine

摘　　要：目的探讨FLT3-ITD及DNMT3A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-ITD及DNMT3A突变,提示预后不良。检测FLT3-ITD及DNMT3A突变状态有助于对AML进行预后评估。Objective To investigate the roles of FLT3-ITD and DNMT3A mutations in the prognosis of acutemyeloid leukemia(AML)patients in intermediate-risk-cytogenetic-group.Methods A total of132de novoAML patients were enrolled from the Affiliated Hospital of Oregon Health and Science University from2010to2016,and they were classified into favorable-risk-cytogenetic-group(24cases),intermediate-risk-cytogeneticgroup(79cases)and adverse-risk-cytogenetic-group(27cases).There were2cases with unknown cytogeneticinformation.Totally,42genes being relevant to hematopoietic malignancies were determined by next generationsequencing(NGS).Results There were91%(120/132)of AML cases with at least one mutation,and the patternof co-mutations(≥2)accounted for61%.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 hada shorter overall survival compared to FLT3-ITD mutation negative group(P<0.001).In the present of DNMT3Awildtype,there was no statistical significance for overall survival between FLT3-ITD mutation positive and FLT3-ITDmutation negative groups(P>0.05).FLT3-ITD mutation positive with DNMT3A mutation group had a shorter overallsurvival 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-ITDand DNMT3A have an adverse prognosis.The determinations of FLT3-ITD and DNMT3A mutations may be needed torefine prognostication and guide clinical management in AML.

关 键 词：FLT3-ITD基因 DNMT3A基因 突变 急性髓系白血病 预后因素 

分 类 号：R446.1[医药卫生—诊断学]