伴JAK2 exon12突变与JAK2 V617F突变真性红细胞增多症患者的临床与实验室特征比较  

Clinical and laboratory features compared between JAK2 exon12 and JAK2 V617F mutated polycythemia vera

作　　者：刘丹 张培红 徐泽锋 马娇 秦铁军 曲士强 孙秀娟 李冰 潘丽娟 贾玉娇 肖志坚 Liu Dan;Zhang Peihong;Xu Zefeng;Ma Jiao;Qin Tiejun;Qu Shiqiang;Sun Xiujuan;Li Bing;Pan Lijuan;Jia Yujiao;Xiao Zhijian(State Key Laboratory of Experimental Hematology,National Clinical Research Center for Blood Diseases,Institute of Hematology&Blood Diseases Hospital,Chinese Academy of Medical Science&Peking Union Medical College,Tianjin 300020,China;Shandong Cancer Hospital and Institute,Shandong First Medical University and Shandong Academy of Medical Sciences,Jinan,250117,China)

机构地区：[1]中国医学科学院血液病医院(中国医学科学院血液学研究所),实验血液学国家重点实验室,国家血液系统疾病临床医学研究中心,天津300020 [2]山东第一医科大学附属肿瘤医院(山东省肿瘤防治研究院、山东省肿瘤医院)淋巴血液科,济南250117

出　　处：《中华血液学杂志》2022年第2期107-114,共8页Chinese Journal of Hematology

基　　金：国家自然科学基金(81530008、81770129、81470297);中国医学科学院医学与健康科技创新工程项目(2016-I2M-1-001、2020-I2M-C&T-B-090);天津市自然科学基金(18JCZDJC34900、19JCQNJC09400)。

摘　　要：目的比较伴JAK2 exon12与JAK2 V617F突变真性红细胞增多症(PV)患者的临床与实验室特征。方法对2013年9月至2020年2月在中国医学科学院血液病医院就诊的570例符合WHO(2016)诊断分型标准且伴有JAK2基因突变的初诊PV患者进行回顾性分析,比较伴有JAK2 exon12与JAK2 V617F基因突变患者的临床与实验室特征。结果①全部570例患者中,543例(95.3%)伴有单纯JAK2 V617F突变(JAK2 V617F组),24例(4.2%)伴有单纯JAK2 exon12突变(JAK2 exon12组),3例(0.5%)伴有JAK2 exon12与JAK2 V617F双突变。②27例伴有JAK2 exon12突变的患者中,JAK2 exon12突变类型包括缺失(10例,37.0%)、缺失伴插入(10例,37.0%)和错义突变(7例,25.9%)。③与JAK2 V617F组比较,JAK2 exon12组患者更年轻[中位年龄50(20~73)岁对59(25~91)岁,P=0.040],RBC[8.19(5.88~10.94)×10^(12)/L对7.14(4.11~10.64)×10^(12)/L,P<0.001]和红细胞比容[64.1%(53.7%~79.0%)对59.6%(47.2%~77.1%),P=0.001]更高,而WBC[8.29(3.20~18.99)×10^(9)/L对12.91(3.24~38.30)×10^(9)/L,P<0.001]、PLT[313(83~1433)×10^(9)/L对470(61~2169)×10^(9)/L,P<0.001]和红细胞生成素[0.70(0.06~3.27)U/L对1.14(0.01~10.16)U/L,P=0.002]更低。④选取性别、年龄匹配的JAK2 exon12组与JAK2 V617F组各20例患者的骨髓活组织病理标本,JAK2 exon12组巨核细胞疏松成簇的患者比例显著低于JAK2 V617F组(40.0%对80.0%,P=0.022),其他骨髓病理形态特性相似。⑤JAK2 exon12组、JAK2 V617F突变组的中位随访时间分别为30(4~83)个月、37(1~84)个月,两组总生存(P=0.422)和无血栓生存(P=0.900)差异无统计学意义。结论JAK2 exon12突变患者较JAK2 V617F突变患者更为年轻,红系增生更显著,骨髓巨核细胞疏松成簇更少见。Objective To compare clinical and laboratory features between JAK2 exon12 and JAK2 V617F mutated polycythemia vera(PV).Method We collected data from 570 consecutive newly-diagnosed subjects with PV and JAK2 mutation,and compared clinical and laboratory features between patients with JAK2 exon12 and JAK2 V617F mutation.Results 543(95.3%)subjects harboured JAK2 V617F mutation(JAK2 V617F cohort),24(4.2%)harboured JAK2 exon12 mutations(JAK2 exon12 cohort),and 3(0.5%)harboured JAK2 exon12 and JAK2 V617F mutations.The mutations in JAK2 exon12 including deletion(n=10,37.0%),deletion accompanied insertion(n=10,37.0%),and missense mutations(n=7,25.9%).Comparing with JAK2 V617F cohort,subjects in JAK2 exon12 cohort were younger[median age 50(20-73)years versus 59(25-91)years,P=0.040],had higher RBC counts[8.19(5.88-10.94)×10^(12)/L versus 7.14(4.11-10.64)×10^(12)/L,P<0.001]and hematocrit[64.1%(53.7-79.0%)versus 59.6%(47.2%-77.1%),P=0.001],but lower WBC counts[8.29(3.2-18.99)×10^(9)/L versus 12.91(3.24-38.3)×10^(9)/L,P<0.001],platelet counts[313(83-1433)×10^(9)/L versus 470(61-2169)×10^(9)/L,P<0.001]and epoetin[0.70(0.06-3.27)versus 1.14(0.01-10.16)IU/L,P=0.002]levels.We reviewed bone marrow histology at diagnosis in 20 subjects with each type of mutation matched for age and sex.Subjects with JAK2 exon12 mutations had fewer loose megakaryocyte cluster(40%versus 80%,P=0.022)compared with subjects with JAK2 V617F.The median follow-ups were 30 months(range 4-83)and 37 months(range 1-84)for cohorts with JAK2 V617F and JAK2 exon12,respectively.There was no difference in overall survival(P=0.422)and thrombosis-free survival(P=0.900).Conclusions Compared with patients with JAK2 V617F mutation,patients with JAK2 exon12 mutation were younger,and had more obvious erythrocytosis and less loose cluster of megakaryocytes.

关 键 词：真性红细胞增多症 JAK2 exon12突变 骨髓活组织病理形态 

分 类 号：R555.1[医药卫生—血液循环系统疾病]