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
陈洋 1谢研研 2方玉 3洪鸣 4刘文洁 4周璇 3张巍 3师锦宁 3钱思轩4
作者信息
- 1. 南京医科大学附属江宁医院血液内科,江苏南京 211100;南京医科大学第一附属医院血液内科,江苏南京 210029
- 2. 南京医科大学附属江宁医院输血科,江苏南京 211100
- 3. 南京医科大学附属江宁医院血液内科,江苏南京 211100
- 4. 南京医科大学第一附属医院血液内科,江苏南京 210029
- 折叠
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FLT3 ITD+、FLT3TKD+、FLT3 ITD++TKD+和 FLT3 ITD-+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FLT3 ITD+、FLT3 ITD-+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FLT3 ITD+、FLT3 TKD+、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FLT3 ITD++TKD+)的总生存期(OS)长于单独FLT3 ITD+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FLT3 TKD+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.
Abstract
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 FLT3 TKD+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Key words
acute myeloid leukemia/FLT3/co-mutated gene/TET2/prognosis引用本文复制引用
基金项目
南京市医学科技发展项目(YKK20200)
出版年
2024
NETL
NSTL
万方数据