Ph阴性骨髓增殖性肿瘤中ASXL1与CALR突变共存的检测及临床意义  

Detection of ASXL1 Mutation and CALR Mutation Coexistance in Patients with Ph Negative Myeloproliferative Neoplasm and Its Clinical Gignificance

作　　者：陈梅玉 沈宏杰[2] 晁红颖[1] 周民[3] 卢绪章[1] 张修文[1] 刘洁[1] 姜乃可[1] 王谦[2] 

机构地区：[1]南京医科大学附属常州市第二人民医院血液科,江苏常州213003 [2]苏州大学附属第一医院血液科,江苏苏州215000 [3]常州市第三人民医院血液科,江苏常州213001

出　　处：《中国实验血液学杂志》2017年第6期1738-1743,共6页Journal of Experimental Hematology

基　　金：国家自然科学基金青年基金(81500103);常州市科技局国际科技合作项目(CZ20140018);常州市高层次卫生人才培养工程(2016CZLJ027)

摘　　要：目的:研究原发性血小板增多(ET)和原发性骨髓纤维化(PMF)患者ASXL1与CALR基因突变共存情况,比较其与单基因突变及突变阴性患者部分临床参数间的差异性。方法:采用基因组DNA-PCR扩增产物直接测序法检测263例ET患者及29例PMF患者ASXL1基因12号外显子、CALR基因9号外显子和MPL基因10号外显子突变;采用等位基因特异性PCR检测JAK2V617F突变情况。结果:292例患者总的突变检出率为72.6%(212/292),ASXL1、CALR、JAK2V617F及MPL基因突变发生率分别为5.8%、30.5%、39.0%及2.4%;5.1%(15/292)的患者同时携带双基因突变,包括ASXL1/CALR(n=11)、ASXL1/JAK2V617F(n=2)、MPL/CALR(n=1)及ASXL1/MPL(n=1),其中ASXL1/CALR突变共存发生率明显高于其它突变类型。与单基因CALR及JAK2V617F突变相比,CALR/ASXL1双突变组的ET患者有更高的血小板水平及较低的血红蛋白水平(P<0.05),但在中位年龄及外周白细胞计数方面无明显差异(P>0.05);与突变阴性组相比,CALR/ASXL1双突变ET组具有较低的白细胞数及血红蛋白水平,但具有较高的血小板水平,差异均有统计学意义(P<0.05);在中位年龄方面差异无统计学意义(P>0.05)。结论:ASXL1与CALR突变共存在ET患者中有较高的检出率,与单基因突变及突变阴性组相比,具有较高的血小板水平及较低的血红蛋白水平。Objective： To explore the coexistence of ASXL1 and CALR gene mutations in patients with essential thrombocytheima（ ET） and with primary myelofibrosis（ PMF）,and to compare the differences of clinical characteristics between ET and PMF patients carrying ASXL1 and CALR mutations,and ET and PMF patients carrying solitary gene mutation,and ET and PMF patients without any mutations. Methods： The mutations of ASXL1 gene at exon 12,CALR gene at exon 9 and MPL gene at exon 10 in 263 essential ET patients and 29 PMF patients were detected by PCR amplification followed by direct sequencing of genomic DNA. The JAK2V617F mutations were used by allele specific PCR detection.Results： 72. 6%（ 212/292） of patients harbored at least one mutation. The incidences of ASXL1 and CALR mutations were5. 8% and 30. 5%,respectively. The frequencies of JAK2V617F and MPL mutations were 3 9. 0% and 2. 4%,respectively. 5. 1%（ 1 5/2 9 2） of patients had double mutations,including ASXL1 and CALR（ n = 11）,ASXL1 and JAK2V617F（ n = 2）,MPL and CALR（ n = 1） and ASXL1 and MPL（ n = 1）. The frequency of concurrent ASXL1 and CALR mutations was found to be high. Significant difference was found on hemoglobin levels and platelet counts between CALR and ASXL1 mutations and single mutation（ P〈0. 05）, however,the difference on leukocyte counts and median age was not found. Compared with negative patients,the presence of ASXL1 and CALR mutations was found to be significantly correlative with lower hemoglobin level（ P = 0. 045）,lower leukocyte count（ P = 0. 002） and with higher platelet counts（ P =0. 001）,but the difference of median age was not found. Conclusion： The frequency of concurrent ASXL1 and CALR mutations is higher in ET patients. The coexistence of ASXL1 and CALR gene mutations significantly associated with lower hemoglobin level and higher platelet count.

关 键 词：ASXL1 CALR 骨髓增殖性肿瘤 原发性血小板增多症 原发性骨髓纤维化 

分 类 号：R551.3[医药卫生—血液循环系统疾病]