JAK2V617F点突变与BCR-ABL阴性骨髓增殖性疾病临床关系研究

Relationship between JAK2 V617F point mutation and clinical characteristics of BCR-ABL negative myeloproliferative diseases patients

目的研究JAK2V617F点突变与BCR-ABL阴性的骨髓增殖性疾病(MPD)患者临床特征的关系。方法选择62例BCR-ABL阴性MPD患者为研究组,包括真性红细胞增多症(PV)26例、原发性血小板增多症(ET)26例、原发性骨髓纤维化(IMF)9例、慢性中性粒细胞白血病(CNL)1例;同时选择慢性粒细胞白血病(CML)20例、急性白血病(AL)10例、健康志愿者15例为对照组。用等位基因特异性聚合酶链反应(AS-PCR)方法结合基因测序检测各组患者JAK2V617F的突变情况,分析JAK2V617F点突变与BCR-ABL阴性的MPD患者临床特征的关系。结果62例BCR-ABL阴性的MPD患者中,44例JAK2V617F突变阳性,其中PV 23例(88.5%,23/26),ET 15例(57.7%,15/26),IMF 5例(55.6%,5/9),CNL 1例;对照组均阴性。JAK2V617F突变阳性的MPD患者和突变阴性的MPD相比较,两组在发病年龄方面差异无统计学意义;在血象方面,两组PV患者的白细胞[(18.2±8.0)×109/Lvs(7.6±1.4)×109/L,P=0.035]、血小板计数[(479±141)×109/L vs(277±102)×109/L,P=0.025]及两组ET患者的血红蛋白[(146±16)g/L vs(122±17)g/L,P=0.001]、白细胞计数[(14.6±5.1)×109/L vs(10.9±3.4)×109/L,P=0.044]差异均有统计学意义。另外,与JAK2V617F突变阴性的ET相比,突变阳性的ET患者出血、血栓、转白等并发症的发生率高(P=0.034)。结论应用AS-PCR法筛选JAK2V617F突变准确率高,可在临床上推广使用。与JAK2V617F突变阴性的ET患者相比较,突变阳性的ET患者的临床过程更具有侵袭性。

Objective To investigate the relationship between JAK2 V617F point mutation and the clinical characteristics of myeloproliferative disease（MPD） patients without BCR-ABL fusion gene. Methods Sixty-two BCR-ABL negative MPD patients [26 polycythemia vera （PV） cases, 26 primary Ethrombocytosis （ET） cases, 9 idiopathic myelofibrosis（IMF） cases and 1 chronic neutrophilic leukemia（CNL） case] were enrolled as study group and the others [20 chronic myelocytic leukemia（CML） cases, 10 acute leukemia（AL） cases and 15 healthy volunteers] served as control group. JAK2V617F point mutation was detected by allele-specific polymerase chain reaction（AS-PCR） method and confirmed by direct sequencing. The relationship between JAK2 V617F point mutation and the clinical characteristics of BCR-ABL negative MPD patients was analysed. Results JAK2 V617F point mutation was detected in 44/62 BCR-ABL negative MPD patients, including 23/26 （88.5 %） PV patients, 15/26 （57.7 %） ET patients, 5/9 （55.6%） IMF patients and one CNL patient. While the somatic JAK2 V617F mutation was not detected in any samples from control group. No difference in the clinical data,in terms of age,was found between JAK2 V617F positive or negative PV, ET and IMF patients, respectively. However, there existed significant difference in leukocyte （18.2±8.0）×10^9/L vs （7.64±1.4）×10^9/L（P=0.035） and platelet counts （479±141）×10^9/L vs （277±102）×10^9/L（P=0.025） between JAK2V617 positive and negative PV patients. The same result was in hemoglobin （146±16） g/L vs （122±17） g/L（P=0.001） and leukocyte counts （14.6±5.1）×10^9/L vs （10.9±3.4）×10^9/L（P=0.044） between JAK2V617 positive and negative ET. More important, significant difference was found in complication of bleeding, thrombosis or transforming to leukemia between JAK2V617 positive and negative ET（P=0.034） patients. Conclusion AS-PCR is a sensitive and reliable technique in detecting JAK2V617F mutation. The clinical characteristics in JAK2V617F positive ET patients were more progressing compared with those in JAK2V617F negative ET patients.