Objective: To investigate the influence of genetic susceptibility genes for myeloid tumors on the clinical characteristics of patients with myeloproliferative neoplasm (MPN).
Methods: Two hundred and thirty-two patients with MPN diagnosed at the Second Hospital of Tianjin Medical University from September 2017 to December 2021 were collected, myeloid neoplasm-related genes were detected by targeted next-generation sequencing, and germline mutations were verified. The clinical characteristics and prognosis of MPN patients with germlines mutations in the genetic susceptibility gene for myeloid neoplasm were analyzed.
Results: The germline mutation carrier rate of myeloid neoplasm genetic susceptibility gene in MPN patients was 21.6% (50/232), and the PV, ET and PMF patients carrying germline mutations of genetic susceptibility gene for myeloid neoplasm were 25/114 (21.9%), 8/69 (11.6%) and 17/49 (34.7%), respectively, among which PMF patients had the highest carrier rate (P=0.01) and were older (P=0.02). The incidence of chromosomal abnormalities in MPN patients carrying the genetic susceptibitity genes for myeloid neoplasm was higher than that in the non-carrier group (26.5% vs 11.8%, P=0.05). Germline mutations in the genetic susceptibility gene of myeloid neoplasm in MPN patients were mainly concentrated in the RAS pathway, and patients with germline mutations in the genetic susceptibility gene of myeloid neoplasm associated with the RAS pathway had shorter survival without AML progression (P<0.0001). The overall survival time in MPN patients with CBL and TP53 germline mutations was shorter than that of non-carrier group (P=0.001; P=0.043).
Conclusion: In MPN, PMF patients are more likely to carry germline mutations in the genetic susceptibility gene for myeloid neoplasm. MPN patients with germline mutations carring the genetic susceptibility gene for myeloid neoplasm are prone to chromosomal abnormalities; Patients with MPN who have germline mutations in the genetic susceptibility gene for myeloid neoplasm in the RAS pathway are more likely to develop AML; CBL and TP53 germline mutations affect the overall survival of MPN patients.
题目: 髓系肿瘤遗传易感基因在骨髓增殖性肿瘤中的临床价值.
目的: 探讨髓系肿瘤遗传易感基因对骨髓增殖性肿瘤(MPN)患者临床特征的影响.
方法: 收集2017年9月至2021年12月就诊于天津医科大学第二医院的232例MPN患者，通过靶向二代测序技术检测髓系肿瘤相关基因，并进行胚系验证，分析携带髓系肿瘤遗传易感基因胚系突变MPN患者的临床特征及生存.
结果: MPN患者髓系肿瘤遗传易感基因胚系突变携带率为21.6%(50/232)，携带髓系肿瘤遗传易感基因胚系突变的PV、ET、PMF患者分别为25/114(21.9%)例、8/69(11.6%)例、17/49(34.7%)例，其中PMF患者携带率最高(P=0.01)，且年龄较大(P=0.02)。携带髓系肿瘤遗传易感基因组的MPN患者较未携带组染色体异常发生率高(26.5% vs 11.8%，P=0.05)。MPN患者髓系肿瘤遗传易感基因胚系突变主要集中在RAS通路，且携带RAS通路相关髓系肿瘤遗传易感基因胚系突变的患者无AML进展生存期较未携带组更短(P<0.001)。携带CBL、TP53胚系突变的MPN患者总生存期较未携带者更短(P=0.001；P=0.043).
结论: MPN中PMF患者更易携带髓系肿瘤遗传易感基因胚系突变；携带髓系肿瘤遗传易感基因胚系突变的MPN患者易发生染色体异常；集中于RAS途径的髓系肿瘤遗传易感基因胚系突变的MPN患者更易进展为AML；CBL、TP53胚系突变影响MPN患者的总生存.
Keywords: disease progression; inheritance of susceptibility genes; myeloproliferative neoplasm.