Gao Shan, Duan Yi-Fan, Zhang Yu-Hui, Teng Guang-Shuai, DU Chen-Xiao, Bai Jie
Department of Hematology, The Second Hospital of Tianjin Medical University, Tianjin 300211, China.
Department of Hematology, The Second Hospital of Tianjin Medical University, Tianjin 300211, China,E-mail:
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2023;31(4):1119-1124. doi: 10.19746/j.cnki.issn.1009-2137.2023.04.029.
To investigate the influence of genetic susceptibility genes for myeloid tumors on the clinical characteristics of patients with myeloproliferative neoplasm (MPN).
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.
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 (=0.01) and were older (=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% 11.8%, =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 (<0.0001). The overall survival time in MPN patients with and germline mutations was shorter than that of non-carrier group (=0.001; =0.043).
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; and germline mutations affect the overall survival of MPN patients.
探讨髓系肿瘤遗传易感性基因对骨髓增殖性肿瘤（MPN）患者临床特征的影响。
收集2017年9月至2021年12月在天津医科大学第二医院确诊的232例MPN患者，采用靶向二代测序检测髓系肿瘤相关基因，并验证胚系突变。分析髓系肿瘤遗传易感性基因发生胚系突变的MPN患者的临床特征及预后。
MPN患者中髓系肿瘤遗传易感性基因的胚系突变携带率为21.6%（50/232），携带髓系肿瘤遗传易感性基因胚系突变的真性红细胞增多症（PV）、原发性血小板增多症（ET）和原发性骨髓纤维化（PMF）患者分别为25/114（21.9%）、8/69（11.6%）和17/49（34.7%），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性基因的MPN患者染色体异常发生率高于非携带组（26.5%对11.8%，P=0.05）。MPN患者髓系肿瘤遗传易感性基因的胚系突变主要集中在RAS通路，与RAS通路相关的髓系肿瘤遗传易感性基因发生胚系突变的患者无急性髓系白血病（AML）进展的生存期较短（P<0.0001）。携带JAK2和CALR胚系突变的MPN患者总生存时间短于非携带组（P=0.001；P=0.043）。
在MPN中，PMF患者更易携带髓系肿瘤遗传易感性基因的胚系突变。携带髓系肿瘤遗传易感性基因胚系突变的MPN患者易发生染色体异常；RAS通路中髓系肿瘤遗传易感性基因发生胚系突变的MPN患者更易发生AML；JAK2和CALR胚系突变影响MPN患者的总生存。
