骨髓增殖性肿瘤患者DTA突变与血栓栓塞关系研究  

Relationship between DTA Mutations and Thromboembolism in Patients with Myeloproliferative Neoplasms

作　　者：王敏 赵红玉 李大启 陈萍 WANG Min;ZHAO Hong-Yu;LI Da-Qi;CHEN Ping(Department of Hematology,Central Hospital Affiliated to Shandong First Medical University,Jinan 250013,Shandong Province,China)

机构地区：[1]山东第一医科大学附属中心医院血液科,山东济南250013

出　　处：《中国实验血液学杂志》2024年第3期819-824,共6页Journal of Experimental Hematology

基　　金：国家自然科学基金(82000125);济南市中心医院2020年度高层次课题培育计划青年项目;2019年济南市卫生健康委员会科技计划项目(2019-1-02)。

摘　　要：目的:分析骨髓增殖性肿瘤(MPN)患者DTA(DNMT3A、TET2和ASXL1)基因突变情况,并探讨DTA突变与血栓栓塞的关系。方法:回顾性分析2016年9月至2022年9月在山东第一医科大学附属中心医院确诊的62例初诊MPN患者的临床资料,采用二代测序检测技术对35种MPN相关基因进行检测,分析MPN患者DTA突变情况及其与血栓栓塞事件的关系。结果:75.8%(47/62)的患者可检测出非驱动基因突变,每个患者的平均突变数为1.08个,发生突变的非驱动基因主要有TET2(38.7%,24/62)、DNMT3A(9.7%,6/62)及ASXL1(6.5%,4/62)。62例MPN患者中31例(50.0%)检出DTA基因突变,主要与驱动基因伴随出现;≥60岁的MPN患者DTA突变率明显高于<60岁的患者(P=0.039)。存在DTA突变的患者血栓栓塞发生率为58.1%(18/31),明显高于无DTA突变的MPN患者(19.4%,6/31)(P=0.002)。发生血栓栓塞的患者的TET2基因突变率为66.7%(16/24),显著高于未发生血栓栓塞患者的TET2基因突变率(21.1%,8/38)(P=0.00)。结论:MPN患者DTA突变发生率较高,主要与驱动基因突变伴随发生。DTA突变的MPN患者血栓栓塞发生率明显高于无DTA突变的患者,尤其是伴有TET2突变的老年患者需警惕血栓栓塞事件的发生。Objective:To analyze the DTA(DNMT3A,TET2,ASXL1)mutations in patients with myeloproliferative neoplasms(MPN),and preliminarily explore their correlation with thromboembolism.Methods:Clinical characteristics of 62 patients diagnosed de novo MPN at Central Hospital Affiliated to Shandong First Medical University from September 2016 to September 2022 were retrospectively analyzed.Next-generation sequencing was used to detect 35 MPN-related genes,and the DTA mutations in MPN patients and their relationship with thromboembolic events were analyzed.Results:75.8%(47/62)of the patients presented pathogenic non-driver mutations,and the mean number of pathogenic non-driver mutations per patient was 1.08.Among them,the most frequently mutated non-driver genes were TET2(38.7%,24/62),DNMT3A(9.7%,6/62)and ASXL1(6.5%,4/62).The presence of DTA gene mutations was 50%(31/62)in the total MPN patients,and mainly accompanied by driver mutations.The mutation rate of DTA in patients aged≥60 years was significantly higher than that in patients<60 years old(P=0.039).The incidence of thromboembolism in patients with DTA mutation was 58.1%(18/31),which was significantly higher than that in patients without DTA mutation(19.4%,6/31)(P=0.002).The TET2 gene mutation rate in MPN patients with thromboembolism was 66.7%(16/24),which was significantly higher than that in patients without thromboembolism(21.1%,8/38)(P=0.00).Conclusion:Patients with MPN have a higher incidence of DTA mutations,which are mainly accompanied by driver gene mutations.The incidence of thromboembolism in MPN patients with DTA mutations is higher than that in patients without DTA mutations.Especially,the elderly(≥60 years)essential thrombocythemia(ET)and polycythemia vera(PV)patients with TET2 mutation should be vigilant for thromboembolic events.

关 键 词：骨髓增殖性肿瘤 二代测序 DTA突变 血栓栓塞 

分 类 号：R733.3[医药卫生—肿瘤]