Ph~-经典型骨髓增殖性肿瘤患者驱动基因突变及其临床分析
|
摘要
目的:探讨Ph~-经典型骨髓增殖性肿瘤(MPN)患者驱动基因突变与临床指标的关系,为MPN诊治及预后判断提供新的观察指标。探寻MPN治疗可能存在新的治疗靶点。方法:回顾性分析2015年1月~2018年6月就诊弋矶山医院门诊及住院的158例MPN患者临床特征,采用等位基因特异性聚合酶链反应(AS-PCR)检测JAK2、MPL突变,直接测序法检测CALR突变。结果:PV组JAK2~+表达的年龄高于JAK2~-表达(P<0.05),JAK2~+表达的WBC和PLT数高于JAK2-表达(P<0.05);ET组JAK2~+表达年龄高于CLAR+和JAK2/MPL/CLAR-表达(P<0.05),JAK2~+表达Hb数高于JAK2/MPL/CLAR-表达(P<0.05);PMF组JAK2~+表达脾大情况高于JAK2/MPL/CLAR-表达(P<0.05)。多因素分析显示WBC增高是PV患者血栓事件的危险因素,高龄、JAK2~+表达和脾大是ET患者血栓事件的危险因素。结论:在Ph~-经典型MPN患者中,患者临床特征与驱动基因突变类型密切相关。
Objective: To investigate the relationship between driving gene mutation and clinical markers in patients with classical Philadelphia-negative myeloproliferative neoplasms( MPN) for the new observational indicators in diagnosis,treatment target and estimation of prognosis of MPN. Methods: The clinical characteristics were retrospectively examined in 158 cases of MPN diagnosed and treated our hospital between January 2015 and June 2018.Allele specific polymerase chain reaction( AS-PCR) was performed to detect JAK2 and MPL mutations,and direct sequencing was used to detect CALR mutation.Results: Compared with patients with JAK2~-expression,significantly higher JAK2~+ expression as well as WBC and PLT was seen in older patients in polycythemia vera( PV) group( P<0. 05).Also,higher JAK2~+ expression was observed in older patients in essential thrombocytosis( ET) group compared to those with CLAR+and JAK2/MPL/CLAR~-expression( P < 0. 05). The number of Hb in patients with JAK2~+ expression was significantly higher than that of patients with JAK2/MPL/CLAR-expression( P<0. 05).Splenomegaly was more frequent in patients with JAK2~+ expression in PMF group as compared with patients with JAK2/MPL/CLAR-expression( P<0. 05).Multivariate analysis showed that increased WBC was a risk factor for thromboembolism in patients with PV.Age,JAK2~+ expression and splenomegaly were risks for thromboembolism in patients with ET.Conclusion: The clinical characteristics of patients with classical Philadelphia-negative MPN are closely related to the type of driving gene mutation.
Objective: To investigate the relationship between driving gene mutation and clinical markers in patients with classical Philadelphia-negative myeloproliferative neoplasms( MPN) for the new observational indicators in diagnosis,treatment target and estimation of prognosis of MPN. Methods: The clinical characteristics were retrospectively examined in 158 cases of MPN diagnosed and treated our hospital between January 2015 and June 2018.Allele specific polymerase chain reaction( AS-PCR) was performed to detect JAK2 and MPL mutations,and direct sequencing was used to detect CALR mutation.Results: Compared with patients with JAK2~-expression,significantly higher JAK2~+ expression as well as WBC and PLT was seen in older patients in polycythemia vera( PV) group( P<0. 05).Also,higher JAK2~+ expression was observed in older patients in essential thrombocytosis( ET) group compared to those with CLAR+and JAK2/MPL/CLAR~-expression( P < 0. 05). The number of Hb in patients with JAK2~+ expression was significantly higher than that of patients with JAK2/MPL/CLAR-expression( P<0. 05).Splenomegaly was more frequent in patients with JAK2~+ expression in PMF group as compared with patients with JAK2/MPL/CLAR-expression( P<0. 05).Multivariate analysis showed that increased WBC was a risk factor for thromboembolism in patients with PV.Age,JAK2~+ expression and splenomegaly were risks for thromboembolism in patients with ET.Conclusion: The clinical characteristics of patients with classical Philadelphia-negative MPN are closely related to the type of driving gene mutation.
引文
[1]ARBER DA,ORAZI A,HASSERJIAN R,et al.The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia[J].Blood,2016,127(20):2391-2405.
[2]FREITAS RM,DA COSTA MARANDUBA CM.Myeloproliferative neoplasms and the JAK/STAT signaling pathway:an overview[J].Rev Bras Hematol Hemoter,2015,37(5):348-353.
[3]TEFFERI A,BARBUI T.Polycythemia vera and essential thrombocythemia:2017 update on diagnosis,risk-stratification,and management[J].Am J Hematol,2017,92(1):94-108.
[4]OKU S,TAKENAKA K,KURIYAMA T,et al.JAK2 V617F uses distinct signalling pathways to induce cell proliferation and neutrophil activation[J].Br J Haematol,2010,150(3):334-344.
[5]PARDANANI AD,LEVIN RL,LASHO T,et al.MPL mutations in myeloprolife-rative and other myeliod disorders:a study 1182 patients[J].Blood,2016,108:3472-3476.
[6]VANNUCCHI AM,ROTUNNO G,BARTALUCCI N,et al.Calreticulin mutation-specific immunostaining in myelopro1iferative neoplasms pathogenetic insight and diagnostic value[J].Leukemia,2014,28(9):181l-1818.
[7]LANGABEER SE.Chasing down the triple-negative myeloproliferative neoplasms:implications for molecular diagnostics[J].Jakstat,2016,5(2-4):e1248011.
[8]TEFERIF A.Myeloproliferative neoplasms:a decade of discoveries and treatment advances[J].Am J Hematol,2016,91(1):50-58.
[9]KLAMPFL T,GISSLINGER H,HARUTYUNYAN AS,et al.Somatic mutations of calreticulin in myeloproliferative neoplasms[J].NEngl J Med,2013,369(25):2379-2390.
[10]BARBUI T,CAROBBIO A,CERVANTES F,et al.Thrombosis inprimary myelofibrosis:incidence and risk factor[J].Blood,2010,115(4):778-782.
[11]BOSE P,ABOU ZAHR A,VERSTOVSEK S.Investigational Janus kinase inhibitors in development for myelofibrosis[J].Expert Opin Investig Drugs,2017,26(6):723-734.
[2]FREITAS RM,DA COSTA MARANDUBA CM.Myeloproliferative neoplasms and the JAK/STAT signaling pathway:an overview[J].Rev Bras Hematol Hemoter,2015,37(5):348-353.
[3]TEFFERI A,BARBUI T.Polycythemia vera and essential thrombocythemia:2017 update on diagnosis,risk-stratification,and management[J].Am J Hematol,2017,92(1):94-108.
[4]OKU S,TAKENAKA K,KURIYAMA T,et al.JAK2 V617F uses distinct signalling pathways to induce cell proliferation and neutrophil activation[J].Br J Haematol,2010,150(3):334-344.
[5]PARDANANI AD,LEVIN RL,LASHO T,et al.MPL mutations in myeloprolife-rative and other myeliod disorders:a study 1182 patients[J].Blood,2016,108:3472-3476.
[6]VANNUCCHI AM,ROTUNNO G,BARTALUCCI N,et al.Calreticulin mutation-specific immunostaining in myelopro1iferative neoplasms pathogenetic insight and diagnostic value[J].Leukemia,2014,28(9):181l-1818.
[7]LANGABEER SE.Chasing down the triple-negative myeloproliferative neoplasms:implications for molecular diagnostics[J].Jakstat,2016,5(2-4):e1248011.
[8]TEFERIF A.Myeloproliferative neoplasms:a decade of discoveries and treatment advances[J].Am J Hematol,2016,91(1):50-58.
[9]KLAMPFL T,GISSLINGER H,HARUTYUNYAN AS,et al.Somatic mutations of calreticulin in myeloproliferative neoplasms[J].NEngl J Med,2013,369(25):2379-2390.
[10]BARBUI T,CAROBBIO A,CERVANTES F,et al.Thrombosis inprimary myelofibrosis:incidence and risk factor[J].Blood,2010,115(4):778-782.
[11]BOSE P,ABOU ZAHR A,VERSTOVSEK S.Investigational Janus kinase inhibitors in development for myelofibrosis[J].Expert Opin Investig Drugs,2017,26(6):723-734.