慢性骨髓增殖性肿瘤患者钙网蛋白基因突变及其临床意义  

Mutation of CALR Gene in Patients with Chronic Myeloproliferative Neoplasm and Its Clinical Significance

作　　者：汤琴[1] 张修文[2] 夏雷[1] 姜乃可[3] 

机构地区：[1]江苏大学附属金坛医院血液科,江苏金坛213200 [2]常州市第二人民医院中心实验室,江苏常州213000 [3]常州市第二人民医院血液科,江苏常州213000

出　　处：《中国实验血液学杂志》2017年第1期151-156,共6页Journal of Experimental Hematology

摘　　要：目的:研究慢性骨髓增殖性肿瘤(MPN)患者钙网蛋白(CALR)基因突变并探讨其临床意义。方法:采集患者外周血,提取基因组DNA,PCR扩增CALR基因第9号外显子和人血小板生成素受体(MPL)基因片段,应用直接测序法检测CALR及MPL基因突变;采用等位基因特异性PCR检测JAK2 17F突变。结果:共检出CALR基因突变13例(23.6%);44例原发性血小板增多症(ET)患者中,检出CALR基因突变10例,发生率为22.7%,其中Ⅰ型(c.1092_1143del52bp)5例、Ⅱ型(c.1154_1155ins5bp)4例、Ⅲ型(c.1094_1139del46bp)1例;11例原发性骨髓纤维化(PMF)患者中,检出CALR突变3例,发生率为27.2%,其中Ⅰ型2例、Ⅱ型1例;共检出JAK2 V617F突变32例(58.1%),包括ET患者26例(59.1%),PMF患者6例(54.5%)。在所有标本中均未检测到MPL W515基因突变,也未检测到任何两种突变共存。ET患者中CALR基因突变者的中位年龄48岁,明显低于JAK2 V617F突变者的中位年龄(64岁);CALR突变者的血小板水平较JAK2 V617F突变者更高,而白细胞和血红蛋白水平更低,差异具有统计学意义(P<0.05)。有效随访35例患者,其中4例发生深静脉血栓,均为JAK2 V617F突变者,无1例CALR突变者发生血栓并发症。对48例患者分析了染色体核型,仅1例CAKR基因I型突变的PMF患者核型异常,未发现特异性染色体异常。结论:CALR突变在JAK2 V617F及MPL W515K突变阴性的ET及PMF患者中有较高的检出率,与JAK2 V617F突变相比,存在CALR突变的ET患者的中位年龄、白细胞和血红蛋白水平更低,而血小板水平更高,但较少出现血栓并发症。Objective：To analyze the CARL gene mutation in the patients with chronic myeloproliferative neoplasm（MPN） and to explore the clinical significance of CALR mutation.Methods;The peripheral blood of patients was collected and the genomic DNA was exacted,the 9 exon of CALR gene and the fragment of human thrombopoetic receptor（MPL） gene were amplified by PCR,the mutation of CALR and MPL genes was detected by using the direct sequencing,the JAK2 V617 F mutation was detected by using allele spicific PCR.Results：The CALR mutations were detected in 13 patients out of 55 MPN patients（23.6%）.The frequency of CALR mutation was 22.7%（10/44） in 44 essential thrombocythemia（ET） patients.A total of 3 types of CALR mutation were identified（type I c.1092_1143del52bp,n =5;type II c.1154_1155insTTGTC,n=4;type 1 c.1094_1139del46bp,n = l）.CALR mutations occurred at a frequency of 27.2%in primary myelofibrosis（PMF）,including type I（n = 2） and type II（n = 1）.The incidence of JAK2 V617 F was 58.1%（32/55）,that in ET and PMF was 59.1%（26/44） and 54.5%（6/11）,respectively.The mutations of MPL W515 were not detectable in all cases,and the simultaneous mutation of CARL and MPL W515 was not detected.The median age of patients with CALR mutation was significantly younger than that of patients with JAK2 mutations（48 vs 64 years of old,P〈 0.05）.The levels of hemoglobin and leukocytes in patients with CARL mutations were significandy lower（P 〈0.05） but the level of plateletes was higher than that in patients with JAK2 V617 F mutations（P 〈0.05）.Deep venous thrombosis occurred in 4 of 35 ET patients with the JAK2 V617 F mutation（n =4）,but did not occurr in the patients with CALR mutation.Karyotype abnormality was detected in only one case among 48 patients by chromosome karyotype analysis.Conclusion;The incidence of CALR mutation is high in ET and PMF patients without JAK2 V617 F and MPL W515 K mutations,which is associated with younger median age,lower leucocyte and hemoglobin

关 键 词：钙网蛋白 DNA突变分析 骨髓增殖性肿瘤 

分 类 号：R551.3[医药卫生—血液循环系统疾病]