研究动态
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FLT3突变的急性髓系白血病患者共突变基因的临床特征及预后相关性。

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

发表日期:2024 Aug
作者: Yang Chen, Yan-Yan Xie, Yu Fang, Ming Hong, Wen-Jie Liu, Xuan Zhou, Wei Zhang, Jin-Ning Shi, Si-Xuan Qian
来源: GENES & DEVELOPMENT

摘要:

探讨共突变基因对FMS样酪氨酸激酶3(FLT3)突变的急性髓系白血病(AML)患者的临床特征及影响。共纳入273例FLT3 AML患者,共突变基因数据收集患者的数据以进一步分析患者的预后。通过PCR扩增产物直接测序和二代测序(NGS)对FLT3及其他常见突变进行定量。当根据从FLT3突变类型来看,TET2、GATA2、NRAS和ASXL1突变频率在4组中差异有统计学意义(均P < 0.05)。当将患者分为等位基因比率(AR)≥0.5和<0.5组时,发现两组间FLT3-ITD、FLT3-ITD-TKD-、NPM1、NRAS和C-kit的频率存在显着差异(所有 P < 0.05)。将患者分为正常组和异常核型组时,发现两组间FLT3-ITD、FLT3-TKD、NPM1、GATA2、C-kit频率差异有统计学意义(均P < 0.05)。合并FLT3-TKD(包括FLT3-ITD TKD)的AML患者的中位总生存期(OS)长于单独合并FLT3-ITD的患者(P < 0.05)。 FLT3 TET2 型 AML 患者的 OS 和无复发生存期(RFS)均短于 FLT3 TET2- 型患者(均 P < 0.05)。共突变基因的突变频率与 FLT3 亚型、核型相关。和增强现实。具有 FLT3-TKD 的 AML 患者比单独具有 FLT3-ITD 的患者具有更长的 OS,而具有 TET2 共突变的患者具有更短的中位 OS 和 RFS。
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.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).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).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.