JAK2^(V617F)基因突变阳性骨髓增殖性肿瘤患者血栓栓塞的影响因素分析  

Analysis of risk factors for thromboembolism in patients with JAK2^(V617F)gene mutation positive myeloproliferative neoplasms

作　　者：张宇卉 滕广帅[1] 马金玉 胡新 杜晨霄 王艳 胡耐博 李艳旗 邵宗鸿 白洁 Zhang Yuhui;Teng Guangshuai;Ma Jinyu;Hu Xin;Du Chenxiao;Wang Yan;Hu Naibo;Li Yanqi;Shao Zonghong;Bai Jie(Department of Hematology,the Second Hospital of Tianjin Medical University,Tianjin 300211,China)

机构地区：[1]天津医科大学第二医院血液科,天津300211

出　　处：《中华医学杂志》2023年第45期3652-3657,共6页National Medical Journal of China

基　　金：国家自然科学基金(82170117、81890990、81970120、82270148);天津市教委科研计划(2022ZD072、2022KJ253)

摘　　要：目的分析JAK2^(V617F)基因突变阳性骨髓增殖性肿瘤(MPN)患者发生血栓栓塞的影响因素。方法回顾性纳入2017年9月至2023年5月天津医科大学第二医院223例JAK2^(V617F)基因突变阳性MPN患者,其中男111例,女112例,年龄[M(Q_(1),Q_(3))]为57(21,66)岁。根据随访时有无血栓栓塞分为血栓组(n=102)和无血栓组(n=121)。统计两组患者临床特点、实验室特征、细胞遗传学等疾病进展及生存情况。截至2023年3月31日,随访时间[M(Q_(1),Q_(3))]为6(3,10)年。应用Cox风险模型对JAK2^(V617F)阳性MPN患者发生血栓栓塞的影响因素进行分析。结果223例JAK2^(V617F)阳性MPN患者中,真性红细胞增多症(PV)144例,原发性血小板增多症(ET)51例,原发性骨髓纤维化(PMF)28例。血栓组患者ASXL1、BCORL1基因突变率分别为19.6%(20/102)、6.9%(7/102),均高于无血栓组的9.1%(11/121)、0.8%(1/121)(均P<0.05)。血栓组患者单核细胞、C反应蛋白(CRP)、白细胞介素(IL)-1β、IL-8、肿瘤坏死因子-β(TNF-β)升高比例均高于无血栓组(均P<0.05)。多因素分析表明,年龄≥60岁(HR=2.132,95%CI:1.376~3.303,P=0.001)、血栓栓塞史(HR=3.636,95%CI:2.121~6.202,P<0.001)、ASXL1突变阳性(HR=2.245,95%CI:1.093~3.231,P=0.022)、TNF-β升高(HR=2.009,95%CI:1.113~3.624,P=0.021)是JAK2^(V617F)阳性MPN患者发生血栓栓塞的影响因素。结论除年龄、血栓栓塞史、ASXL1突变阳性外,TNF-β升高也是JAK2^(V617F)阳性MPN患者发生血栓栓塞的影响因素,干预炎症可能对防治血栓栓塞有一定的作用。Objective To analyze the risk factors of thrombosis in patients with JAK2^(V617F)mutation positive myeloproliferative neoplasms(MPN).Methods A total of 223 MPN patients with JAK2^(V617F)mutation in the Second Hospital of Tianjin Medical University from September 2017 to May 2023 were retrospectively enrolled,including 111 males and 112 females,aged[M(Q_(1),Q_(3))]57(21,66)years.According to the presence or absence of thromboembolism during follow-up,the patients were divided into thrombosis group(n=102)and non-thrombosis group(n=121).The clinical characteristics,laboratory characteristics,cytogenetics and other disease progression and survival of the two groups of patients were analyzed.As of March 31,2023,the follow-up period[M(Q_(1),Q_(3))]was 6(3,10)years.The influencing factors of thrombosis in JAK2^(V617F)positive MPN patients were analyzed by using the Cox risk model.Results Among 223 JAK2^(V617F)positive MPN patients,144 were polycythemia vera(PV),51 were essential thrombocythemia(ET)and 28 were primary myelofibrosis(PMF).The mutation rates of ASXL1 and BCORL1 genes in the thrombosis group were 19.6%(20/102)and 6.9%(7/102),respectively,which were higher than those in the non-thrombosis group[9.1%(11/121)and 0.8%(1/121)](both P<0.05).The proportion of monocytes,C-reactive protein(CRP),interleukin-1β(IL)-1β,IL-8 and tumor necrosis factor-β(TNF-β)increased in the thrombosis group were higher than those in the non-thrombosis group(all P<0.05).Multivariate analysis showed that age≥60 years(HR=2.132,95%CI:1.376-3.303,P=0.001),history of thrombosis(HR=3.636,95%CI:2.121-6.202,P<0.001),ASXL1 mutation positive(HR=2.245,95%CI:1.093-3.231,P=0.022)and elevated TNF-β(HR=2.009,95%CI:1.113-3.624,P=0.021)were risk factors for thrombosis in JAK2^(V617F)positive MPN patients.Conclusions In addition to age,history of thrombosis and positive ASXL1 mutation,elevated TNF-βis also an influencing factor of thrombosis in JAK2^(V617F)positive MPN patients.Intervention of inflammation may have a certain effect on the preventi

关 键 词：骨髓增殖性肿瘤 血栓栓塞 炎症 影响因素 

分 类 号：R733.3[医药卫生—肿瘤]