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.
题目: 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.
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 +、FLT3 -TKD +、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FLT3- TKD + 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FLT3- ITD +患者，伴TET2共突变患者的中位OS和RFS较短。.
Keywords:
acute myeloid leukemia;