伴FLT3突变的急性髓系白血病患者共突变基因的临床特征及与预后的关系  

Clinical Characteristics and Prognostic Relevance of Co-Mutated Genes in Acute Myeloid Leukemia Patients with FLT3 Mutations

作　　者：陈洋 谢研研 方玉 洪鸣 刘文洁 周璇 张巍 师锦宁 钱思轩 CHEN Yang;XIE Yan-Yan;FANG Yu;HONG Ming;LIU Wen-Jie;ZHOU Xuan;ZHANG Wei;SHI Jin-Ning;QIAN Si-Xuan(Department of Hematology,The Affiliated Jiangning Hospital of Namjing Medical University,Nanjing 211100,Jiangsu Province,China;Deparment of Hematology,The First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,Jiangsu Province,China;Deparment of Blood Traungfusion,The Affiliated Jiangning Haspital of Nanjing Medical University,Namjing 11100,Jiangsu Province,China)

机构地区：[1]南京医科大学附属江宁医院血液内科,江苏南京211100 [2]南京医科大学第一附属医院血液内科,江苏南京210029 [3]南京医科大学附属江宁医院输血科,江苏南京211100

出　　处：《中国实验血液学杂志》2024年第4期1032-1038,共7页Journal of Experimental Hematology

基　　金：南京市医学科技发展项目(YKK20200)。

摘　　要：目的:探讨伴有FLT3突变的初诊急性髓系白血病(AML)患者共突变基因的临床特征及其对患者预后生存的影响。方法:273例FLT3突变的AML患者纳入研究,收集患者的共突变基因资料,进一步对患者预后进行分析。FLT3等常见基因突变用PCR扩增产物直接测序和二代测序定量。结果:按FLT3突变的类型进行分组,分为FLT3ITD^(+)、FLT3TKD+、FLT3ITD^(+)+TKD+和FLT3ITD^(-)+TKD^(-)组,其中TET2、GATA2、NRAS和ASXL1在4组间突变频率不同(均P<0.05);按FLT3突变的等位基因比率(AR)分组,分为AR≥0.5和<0.5两组,其中FLT3ITD^(+)、FLT3ITD^(-)+TKD^(-)、NPM1、NRAS和C-kit在两组间突变频率具有统计学差异(均P<0.05);按染色体核型进行分组,分为正常核型组和异常核型组,其中FLT3ITD^(+)、FLT3TKD+、NPM1、GATA2、C-kit在两组间突变频率不同(均P<0.05)。伴有FLT3TKD+AML患者(包括FLT3ITD^(+)+TKD+)的总生存期(OS)长于单独FLT3ITD^(+)的患者(P<0.05),FLT3^(+)+TET2^(+)AML患者的中位OS及无复发生存期(RFS)均短于FLT3^(+)+TET2-患者(均P<0.05)。结论:共突变基因的突变频率与FLT3亚型、核型和等位基因比例有关。伴有FLT3TKD+AML患者的OS长于单独FLT3ITD^(+)患者,伴TET2共突变患者的中位OS和RFS较短。Objective:To investigate the clinical characteristics and influence of co-mutated gene on acute myeloid leukemia patients(AML)with FMS-like tyrosine kinase-3(FLT3)mutations.Methods:A total of 273 FLT3^(+)AML patients were enrolled,and the co-mutation gene data of the patients were collected to further analyze the prognosis of the patients.FLT3 and other common mutations were quantified by PCR amplification products direct sequencing and second-generation sequencing(NGS).Results:When patients were divided into FLT3 ITD^(+),FLT3 TKD^(+),FLT3 ITD^(+)+TKD^(+)and FLT3 ITD^(-)+TKD^(-)group according to the type of FLT3 mutations,it was found that the frequencies of TET2,GATA2,NRAS and ASXL1 mutation were significantly different among the 4 groups(all P<0.05).When patients were divided into allelic ratio(AR)≥0.5 and<0.5 group,it was found that the frequencies of FLT3 ITD^(+),FLT3 ITD^(-)+TKD^(-),NPM1,NRAS and C-kit were significantly different between the two groups(all P<0.05).When patients were divided into normal and abnormal karyotype group,it was found that the frequencies of FLT3 ITD^(+),FLT3 TKD^(+),NPM1,GATA2 and C-kit were significantly different between the two groups(all P<0.05).The median overall survival(OS)of AML patients with FLT3 TKD^(+)(including FLT3 ITD^(+)+TKD^(+))was longer than that of patients with FLT3 ITD^(+)alone(P<0.05).The OS and relapse-free survival(RFS)of AML patients with FLT3^(+)+TET2^(+)were both shorter than those of patients with FLT3^(+)+TET2^(-)(both P<0.05).Conclusion:The mutation frequencies of co-mutated genes are correlated with subtypes of FLT3,karyotype and AR.AML patients with FLT3TKD^(+)have longer OS than patients with FLT3 ITD^(+)alone,and patients with co-mutation of TET2 have shorter median OS and RFS.

关 键 词：急性髓系白血病 FLT3 共突变基因 TET2 预后 

分 类 号：R733.71[医药卫生—肿瘤]