208例BCR/ABL1阴性慢性骨髓增殖性疾病JAK2、CALR、MPL基因突变检测及其诊断价值  

Detection and Diagnostic Values of JAK2, CALR, MPL Gene Mutations in 208 Cases of BCR/ABL1 Negative Chronic Myeloproliferative Diseases

作　　者：李振玲[1] 高丽[1] 张辉[1] 张春霞[1] 陈艳荣[1] 黄泛舟[1] 龚明[1] 高亚玥[1] 唐寅[1] 马一盖[1] LI Zhen-Ling;GAO Li;ZHANG Hui;ZHANG Chun-Xia;CHEN Yan-Rong;HUANG Fan-Zhou;GONG Ming;GAO Ya-Yue;TANG Yin;MA Yi-Gai(Department of Hematology,China-Japan Friendship Hospital,Beijing100029,China)

机构地区：[1]中日友好医院血液科,北京100029

出　　处：《中国实验血液学杂志》2018年第4期1122-1128,共7页Journal of Experimental Hematology

摘　　要：目的:检测经典BCR/ABL1阴性慢性骨髓增殖性疾病患者JAK2、CALR、MPL基因突变,探讨其诊断价值。方法:2012年3月至2015年12月208例BCR/ABL1阴性慢性骨髓增殖性疾病患者(ET146例,PV37例,MF25例)纳入BCR/ABL1阴性CMPN组,124例继发性血小板增多及73例继发性红细胞增多症患者纳入对照组。抽取骨髓或静脉血提取基因组DNA及总RNA,进行JAK2基因外显子12至20,MPL基因外显子10以及CALR基因外显子3至9测序分析。结果:146例ET患者中,JAK2V617F突变86例(58.9%);JAK2 exon 12突变2例(1.4%);CALR突变41例(28.1%),其中Ⅰ型(c.1092_1143del)22例,Ⅱ型(c.1154_1155insTTGTC)11例,Ⅴ型(c.1091_1142del)1例,Ⅷ型(c.1104_1137del)1例,41型(c.1107_1137del)1例,42型(c.1125_1125del)1例,其他(c.1107_1115del,c.1111_1144 del,c.1101 A>C,c.1112_1117del)4例;MPL基因突变9例(6.2%)。JAK2、CALR、MPL基因突变均阴性的患者有8例(5.4%)。37例PV中检出JAK2以及CALR突变共35例(94.6%),其中JAK2V617F突变31例(83.8%),JAK2 exon 12突变2例(5.4%);CALR突变2例(5.4%),其中Ⅰ型1例,另1例为CALR c.1191_1193del。JAK2、CALR、MPL突变均阴性2例。25例MF中检出JAK2V617F突变19例(76%),CALR突变2例(8%);JAK2、CALR、MPL突变均阴性的患者有4例(16%)。124例继发性血小板增多的患者以及73例继发性红细胞增多的患者中,均未检测出JAK2、CALR或者MPL基因突变。结论:联合JAK2、CALR、MPL基因突变能覆盖大多数BCR/ABL1阴性的骨髓增殖性疾病患者,CALR突变在ET患者中检出率较高,因此CALR突变可作为JAK2、MPL突变阴性的ET的新诊断指标。Objective： To detect the JAK2, CALR and MPL gene mutations in patients with BCR/ABL1 negative chronic myeloproliferative diseases（BCR/ABL1-CMPD）and to evaluate their diagnostic value. Methods： Two hundred and eight cases of BCR/ABL1-CMPD comprising of 146 cases of essential thrombocythemia（ET）, 37 cases of polycythemia vera（PV）and 25 cases of primary myelofibrosis（PMF）from March 2012 to December 2015 were enrolled in the BCR/ABL1-CMPD, while 124 cases of secondary thrombocythemia and 73 cases of secondary polycythemia were enrolled in the control group. The genomic DNA and total RNA Were isolated from bone marrow or peripheral blood, then the exons 12 to 20 of JAK2 gene, exon 10 of MPL gene and exons 3 to 9 of CALR gene were analyzed by using DNA sequencing. Results： among 146 ET patients, the JAK2, CALR or MPL mutations were found in： 138 cases（94.5%）including 86 cases with JAK2 V617 F mutation（58.9%）and 2 cases（1.4%）with exon 12 of JAK2 mutations. CALR mutations were detected in 41 cases（28.1%）, among them type 1（c.1092_1143 del）in22 cases, type 2（c.1154_1155 insTTGTC）in 11 cases, and type 5（c. 1091_1142 del）, type 8（c.1104_1137 del）,type 41（c.1107_1137 del）, type 42（c.1125_1125 del）in one case respectively. In addition, 4 cases were detected withother mutations of the CALR gene（c.1107_1115 del, c.1111_1144 del, c.1101 AC, c.1112_1117 del）. Moreover, 9 cases harbored MPL mutations（6.2%）. Secondly, 31 patients were detected with JAK2 V617 F mutation（83.8%）in37 cases of PV, and JAK2 exon 12 mutations were found in 2 cases（5.4%）. Besides, CALR mutations were detected in2 cases（5.4%）, including 1 case of type I, the other of novel mutation of CALR. Thirdly, 19 in 25 cases of PMF were detected with JAK2 V617 F mutation（76%）, 2 cases with CALR mutations（8%）. 4 patients（16%）, JAK2, CALR or MPL mutations were not detected, but among them 3 cases were found harboring other genetic abnormalities. Fourthly,no mutations of JAK2,

关 键 词：BCR/ABL1阴性慢性骨髓增殖性疾病 原发性血小板增多症 真性红细胞增多症 原发性骨髓纤维化 JAK2基因 CALR基因 MPL基因 

分 类 号：R551.3[医药卫生—血液循环系统疾病]