CAJ | 학술논문

目的探讨细胞因子信号转导抑制蛋白(suppressor of cytokine signaling,SOCS)基因超甲基化在经典型骨髓增殖性肿瘤(MPD)中的临床作用及其机制.方法采用甲基化特异性PCR方法检测SOCS1、2、3基因CpG岛甲基化发生情况,直接测序法检测100例MPD患者JAK2V617F突变情况,用实时定量PCR方法检测SOCS1、2、3的mRNA表达情况.结果 100例MPD患者中有27例(27％)存在SOCS1基因超甲基化,9例(9％)存在SOCS2基因超甲基化,34例(34％)存在SOCS3基因超甲基化.在100例MPN患者中,64例(64％) JAK2V617F突变阳性.MPD患者中SOCS1和SOCS3基因超甲基化组与未甲基化组相比,其SOCSl和SOCS3基因mRNA表达量明显减少(P＜0.05)；SOCS1和SOCS3基因JAK2V617F突变组与野生型组相比,其SOCS1和SOCS3基因mRNA表达量明显减少(P＜0.05).结论 MPD患者中存在JAK2V617F突变及SOCS基因超甲基化,且JAK2V617F突变和SOCS基因甲基化导致SOCS mRNA表达水平降低,SOCS超甲基化和JAK2V617F突变可改变JAK-STAT信号通路等的转录活性而最终影响疾病的发展,这些改变可能代表了一种潜在的治疗方向.
목적 탐토세포인자신호전도억제단백(suppressor of cytokine signaling,SOCS)기인초갑기화재경전형골수증식성종류(MPD)중적림상작용급기궤제.방법 채용갑기화특이성PCR방법검측SOCS1、2、3기인CpG도갑기화발생정황,직접측서법검측100례MPD환자JAK2V617F돌변정황,용실시정량PCR방법검측SOCS1、2、3적mRNA표체정황.결과 100례MPD환자중유27례(27％)존재SOCS1기인초갑기화,9례(9％)존재SOCS2기인초갑기화,34례(34％)존재SOCS3기인초갑기화.재100례MPN환자중,64례(64％) JAK2V617F돌변양성.MPD환자중SOCS1화SOCS3기인초갑기화조여미갑기화조상비,기SOCSl화SOCS3기인mRNA표체량명현감소(P＜0.05)；SOCS1화SOCS3기인JAK2V617F돌변조여야생형조상비,기SOCS1화SOCS3기인mRNA표체량명현감소(P＜0.05).결론 MPD환자중존재JAK2V617F돌변급SOCS기인초갑기화,차JAK2V617F돌변화SOCS기인갑기화도치SOCS mRNA표체수평강저,SOCS초갑기화화JAK2V617F돌변가개변JAK-STAT신호통로등적전록활성이최종영향질병적발전,저사개변가능대표료일충잠재적치료방향.
Objective To investigate the clinical role of hypermethylation of suppressor of cytokine signaling (SOCS) on typical myeloproliferative dieses(MPD) patients and its mechanism.Methods Methylation specific PCR was used to detect SOCS1,2,3 methylation,direct DNA sequencing was performed to detect JAK2V617F mutation,real-time fluorescence quantitative PCR were applied to evaluate transcriptional activity of SOCS1,2,3.Results Among 100 MPD patients,hypermethylation of SOCS1 was detected in 27(27％),hypermethylation of SOCS2 in 9(9％ ),hypermethylation of SOCS3 in 34(34％ ) ; JAK2V617F mutation in 64 (64％).Hypermethylation of SOCS1,3 greatly inhibited gene expression compared with unmethylated ones (P ＜ 0.05 ).Presence of JAK2V617F mutation markedly down-regulated SOCS1,3 gene mRNA expression compared with wild JAK2V617F( P ＜ 0.05).Conclusion Hypermethylation of SOCS1,3 and JAK2V617F mutation exist in MPD,which inhibited SOCS1,3 gene expression.SOCS hypermethylation and JAK2V617F mutation can activate JAK - STAT signaling pathways,these observations may provide a potential therapeutic direction.