132例BCR-ABL融合基因阴性骨髓增殖性肿瘤患者JAK2、CALR及MPL基因突变的临床分析

摘要

目的:探讨 BCR-ABL融合基因阴性的骨髓增殖性肿瘤(myeloproliferative neoplasms,MPN)患者JAK2、CALR及MPL基因突变情况及临床特征.方法:选取132例BCR-ABL融合基因阴性的MPN患者,其中真性红细胞增多症(polycythemia vera,PV)27例,原发性血小板增多症(essential thrombocythemia,ET)97例,原发性骨髓纤维化(primary myelofibrosis,PMF)8例.骨髓抽提DNA,荧光定量PCR检测JAK2、CALR及MPL基因突变情况并分析临床特征,JAK2基因包含 JAK2V617F、JAK2 N542＿E543del、E543＿D544del和 JAK2 K539L1/L2;CALR基因包含CALR L367fs*46和CALR K385fs*47,MPL基因包含MPL W515K/A/L/R1/R2/S和MPL S505N.结果:在132例BCR-ABL融合基因阴性的MPN患者中,仅有JAK2V617F、MPL W515K/A/L/R1/R2/S、CALR L367fs*46和 CALR K385fs*47突变,突变率分别为48.48%(64/132)、0.76%(1/132)、10.61%(14/132)和6.06%(8/132),并且这几种突变不同时出现.PV中仅有JAK2V617F突变,突变 率为74.07%(20/27),ET中JAK2V617F、CALR L367fs*46和CALR K385fs*47突变率分别为42.27%(41/97)、13.40%(13/97)、8.25%(8/97),PMF中 JAK2V617F、CALR L367fs*46和MPL W515K/A/L/R1/R2/S突变率分别为37.50%(3/8)、12.50%(1/8)和12.50%(1/8).在PV患者中,JAK2V617F突变阳性患者的白细胞(white blood cell,WBC)显著高于阴性患者(P＜0.05).在ET患者中,JAK2V617F突变阳性患者的血红蛋白(hemoglobin,Hb)显著高于阴性患者(P＜0.05),CALR突变阳性患者的血小板(platelet,PLT)显著高于阴性患者(P＜0.05).结论:基因检测为MPN的诊断及预后能提供更加方便、准确地依据,为相关的治疗提供更多的帮助.%Objective:To explore the mutations and clinical features of JAK2,CALR and MPL,and the myelopro-liferative neoplasms(MPN)patients with BCR-ABL fusion gene negative were selected.Methods:A total of 132 MPN patients with BCR-ABL fusion gene negative were selected,including 27 cases of polycythemia vera(PV),97 cases of essential thrombocythemia(ET),and 8 cases of primary myelofibrosis(PMF).Then genomic DNA from bone marrow cells was extracted from 132 patients,then the JAK2,CALR and MPL gene mutation were tested with fluores-cence quantitative PCR and clinical features were analysed.The tested JAK2 gene contained JAK2V617F,JAK2 N542＿E543del,E543＿D544del and JAK2 K539L1/L2.CALR gene contained CALR L367fs*46 and CALR K385fs*47, and MPL gene include MPL W515K/A/L/R1/R1/R2/S and MPL S505N.Results:Among 132 MPN patients with BCR-ABL fusion gene negative,the positive mutation rates of JAK2V617F,MPL W515K/A/L/R1/R2/S,CALR L367fs*46 and CALR K385fs*47 respectively were 48.48%(64/132),0.76%(1/132),10.61%(14/132)and 6.06%(8/132),and these kinds of mutations did not appeared at the same time,besides the other mutations were negative.In PV patients,the mutation rate of JAK2V617F was 74.07%(20/27).In ET patients,the mutation rates of JAK2V617F,CALR L367fs*46 and CALR K385fs*47 were 42.27%(41/97),13.40%(13/97),and 8.25%(8/97)respectively.In PMF patients,the mutation rates of JAK2V617F,CALR L367fs*46 and MPL W515K/A/L/R1/R2/S respectively were 37.50%(3/8),12.50%(1/8)and 12.50%(1/8).In the PV patients,white blood cell (WBC)of JAK2V617F mutation-positive patients were significantly higher than negative patients(P＜0.05).In the ET patients,hemoglobin(Hb)of JAK2V617F mutation-positive patients were significantly higher than negative pa-tients(P＜0.05),and platelet(PLT)for CALR mutation-positive were significantly higher than negative patients(P＜0.05).Conclusion:Genetic testing can provide more convenient and accurate for the diagnosis and prognosis of MPN,and provide more help for the related treatment.