常见JAK2基因突变的筛检及在BCR-ABL阴性骨髓增殖病中的临床意义  

The clinical significance of the screening detection of several JAK2 mutations in BCR-ABL negative myeloproliferative diseases patients

作　　者：徐修才[1] 伍权[1] 郑南[1] 丁凯阳[2] 刘欣[2] 

机构地区：[1]安徽医科大学附属省立医院中心实验室,安徽合肥230001 [2]安徽医科大学附属省立医院血液科,安徽合肥230001

出　　处：《中国实验诊断学》2014年第4期557-560,共4页Chinese Journal of Laboratory Diagnosis

摘　　要：目的建立多重等位基因特异性聚合酶链反应检测JAK2基因5种常见突变的方法,并评价在3种常见的骨髓增殖性疾病中的临床意义。方法对149例BCR-ABL融合基因为阴性的骨髓增殖性疾病(MPD)患者,包括73例真性红细胞增多症(PV)、51例原发性血小板增多症(ET)和25例原发性骨髓纤维化(IMF)患者;并结合临床及实验室其他检查资料,对其在该类疾病诊断和鉴别诊断中的价值进行评估。20名急性白血病患者和15名健康志愿者作为对照组进行研究。所有病例的骨髓或外周血标本抽提DNA后用建立的多重PCR方法进行平行检测。结果①149例MPD患者中共检出118例患者存在JAK2基因突变,总突变率为79.2%。其中PV患者阳性68例,JAK2V617F突变65例、JAK2exon12突变3例,阳性率93.2%(68/73);ET患者检测出阳性35例,其中34例为V617F突变,JAK2exon12突变1例,阳性率为68.6(35/51);IMF患者阳性15例,均为JAK2V617F突变,阳性率为60%(15/25)。②JAK2突变阳性的MPD患者和突变阴性MPD的临床资料相比较,两组在患者性别,发病年份方面的差异无统计学意义。研究发现两组PV患者的白细胞[(19.5士7.6)×109/L vs(7.1土1.1)×109/L,P=0.0005]、血小板计数[(498士172)×109/L vs(206士114)×109/L,P=0.0004]、ET患者的血红蛋白[(152士18)g/L vs(112士11)g/L,P<O.OO01]、白细胞计数[(16.2士5.2)×109/L vs(9.3士3.4)×109/L,P<0.0001]以及IMF患者的白细胞[(15.1士3.8)×109/L vs(9.3土1.6)×109/L,P=0.0001]差异均有统计学意义。结论建立的多重PCR方法可以同时检测5种JAK2基因突变,可在临床上推广使用。与JAK2突变阴性的MPD患者相比较,突变阳性的患者有更明显的骨髓增殖紊乱特征。Objective To establish the multiply PCR screening method of JAK2 and evaluate its clinical significance in patients with Myeloproliferative Disease （MPD）.Methods 149 BCR-ABL negative myeloproliferative diseases （MPD）[73 polycythemia vera （PV）cases.51 primary Ethrombocytosis （ET）cases,25 myelofibrosis（lIMF）cases] were enrolled as study group;20 acute leukemia patients and 15 health individuals were enrolled as control group.Ge-nomic DNA from bone marrow or peripheral blood mononuclear cells was extracted and the JAK2 gene mutations of these subjects were detected by multiply AS-PCR.The clinical significance of JAK2 gene mutations and the potential usability of multiply AS-PCR were assessed,based on the clinical data of these patients.Results JAK2 mutations were＆amp;nbsp;detected in 118/149 BCR-ABL negative MPD patients,including 68/73 （93.2%,including 2 patients with JAK 2 ex-on12 mutation ）PV patients,35/51 （68.6%,including 1 patients with JAK 2 exon12 mutation）ET patients and 15/25 （60.0 %）IMF patients.While the somatic JAK 2 mutations were not detected in any samples from control group.No difference in the clinical data in terms of age and sex was found between positive and negative MPD patients.However, there existed significant differences in leukocyte of PV patients [（19.5 ±; 7.6）×109/L vs （7.1 ±; 1.1）×109/L,P =0. 0005],platelet counts of PV patients [（498 ±; 172）×109/L vs （206 ±; 114）×109/L,P =0.0004],hemoglobin level of ET patients [（152 ±; 18）g/L vs （112 ±; 11）g/L,P 〈0.0001 ,leukocyte counts of ET patients [（16.2 ±; 5.2）×109/L vs（9.3 ±; 3.4）× 109/L,P 〈0.0001]and IMF patients [（15.1±; 3.8）× 109/L vs （9.3 ±; 1.6）× 109/L,P =0. 0001]between JAK 2 posit＆#237;ve and negative MPD patients.Conclusion Multiply As-PCR is one sensitive and reliable technique in detecting JAK 2 gene mutations.The clinical characters in JAK 2 positive MPD patients were more pro-gressing compared with those in JAK 2 negative patients.

关 键 词：骨髓增殖性疾病 JAK2 exon12 突变 聚合酶链反应 

分 类 号：R440[医药卫生—诊断学]