首页|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

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

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

acute myeloid leukemiaFLT3co-mutated geneTET2prognosis

陈洋、谢研研、方玉、洪鸣、刘文洁、周璇、张巍、师锦宁、钱思轩

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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

南京医科大学附属江宁医院输血科,江苏南京 211100

急性髓系白血病 FLT3 共突变基因 TET2 预后

南京市医学科技发展项目

YKK20200

2024

中国实验血液学杂志
中国病理生理学会

中国实验血液学杂志

CSTPCD北大核心
影响因子:0.988
ISSN:1009-2137
年,卷(期):2024.32(4)