Objective: This study aimed to investigate the clinical and prognostic significance of TET2 single nucleotide polymorphism I1762V in patients with acute myeloid leukemia (AML) . Methods: The high-throughput sequencing method was used to sequence 58 hematological tumor-related genes in bone marrow samples from 413 patients with AML. TET2 I1762V and other somatic mutations were annotated and compared with patients' clinical information and prognosis. Results: I1762V was found in 154 patients with AML, which was significantly different from the general population in NyuWa Chinese Population Variant Database (χ(2)=72.4, P<0.001) . I1762V was not related to sex, age, and karyotype of patients with AML (P>0.05) . Patients with I1762V had a significantly higher proportion of NPM1 and KIT gene mutations than others (P<0.001) . NPM1 and KIT mutations were mutually exclusive. The survival analysis results revealed that the overall survival (OS) and progression-free survival (PFS) of patients with AML with I1762V were significantly greater than those of wild-type patients (HR=0.57, P=0.030; HR=0.55, P=0.020) , whereas the OS and PFS in patients with AML with DNMT3A mutation (with or without I1762V mutation) were lower than those of wild-type patients (HR=1.79, P=0.030; HR=1.74, P=0.040) . Conclusion: TET2 SNP I1762V has been linked to AML. I1762V is a prognostic factor of patients with AML, which can be used to guide the treatment and evaluate the prognosis of AML.
目的： 探讨TET2单核苷酸多态性（SNP）位点I1762V在急性髓系白血病（AML）患者中的临床意义及其对预后的影响。 方法： 采用高通量测序方法，对2016年7月至2019年12月于河南省肿瘤医院血液科就诊的413例AML患者骨髓样本中的58种血液肿瘤相关基因进行靶向测序。统计TET2 SNP位点I1762V的检出情况，并分析其与患者的临床特征、体细胞突变、预后的相关性。 结果： 154例AML患者检出TET2 SNP位点I1762V，检出比例为37.3%，与公共数据库（NyuWa Chinese Population Variant Database，NCVD）对照人群相比差异有统计学意义（χ(2)＝72.4，P<0.001）；TET2 SNP位点I1762V与AML患者的性别、年龄、染色体核型等均无明显相关性（P值均>0.05）。携带TET2 SNP位点I1762V的患者伴发NPM1基因突变和KIT基因突变的比例显著高于非携带者（P<0.001），且NPM1和KIT突变互斥发生。生存分析结果显示，携带TET2 SNP位点I1762V的AML患者总生存（OS）率、无进展生存（PFS）率显著高于野生型患者（HR＝0.57，P＝0.030；HR＝0.55，P＝0.020）；不论是否携带TET2 SNP位点I1762V，DNMT3A突变的AML患者OS率、PFS率均低于野生型患者（HR＝1.79，P＝0.030；HR＝1.74，P＝0.040）。 结论： TET2 SNP位点I1762V可能与AML相关，可用于指导治疗和预后评估。TET2 SNP位点I1762V是影响AML患者预后的有利因素。.
Keywords: Gene mutation; Gene, TET2; Leukemia, myeloid, acute; Single nucleotide polymorphism.