中文摘要：

目的探讨细胞因子信号转导抑制蛋白（suppressorofcytokinesignaling,SOCS）在经典型骨髓增殖性肿瘤（myeloproliferative neoplasms,MPNs）中的临床作用及其机制。方法采用实时定量PCR检测SOCS1的表达情况,DNA直接测序法检测SOCS1基因突变,甲基化特异性PCR检测SOCS1甲基化发生情况,旨在研究SOCS1在MPNs患者发病机制中的作用,以期为该疾病的诊断和治疗探索新的途径。结果 100例MPNs患者中有37例（37%）存在SOCS1基因甲基化,44例polycythemia vera（PV）有15例（34%）存在SOCS1基因甲基化,48例essential thrombocythemia（ET）有19例（38%）存在SOCS1基因甲基化,8例primary myelofibrosis（MF）有3例（37.5%）存在SOCS1基因甲基化;对照组病例共173例患者中有21例（12%）存在SOCS1基因甲基化：93例Chronic myelocytic leukemia（CML）有15例（16%）存在SOCS1基因甲基化,30例myelodysplastic syndrome（MDS）有4例（13.3%）存在SOCS1基因甲基化,30例acute myeloblastic leukemia（AML）有2例（6.7%）存在SOCS1基因甲基化,20例健康志愿者未发现有SOCS1基因甲基化;MPNs患者中SOCS1基因甲基化组与正常对照组相比,其SOCS1基因的表达量明显减少（P〈0.05）,表明SOCS1基因甲基化可导致SOCS1基因基因表达降低;SOCS1甲基化患者的白细胞计数高于非甲基化患者（P〈0.05）,SOCS1甲基化的MPNs患者较非甲基化患者更易进展为典型MPNs,无甲基化患者未见外周血计数、年龄的相关性;SOCS1基因全序列测序未发现突变。结论 MPNs患者中存在SOCS1基因甲基化,且甲基化导致其基因表达降低,提示SOCS1基因甲基化对疾病发展有提示作用;SOCS1基因甲基化与MPNs患者年龄、外周血细胞计数相关;SOCS1超甲基化可激活JAK-STAT信号通路或伴JAK2突变,这些改变可能代表了一种潜在的治疗方向。

英文摘要：

Objective To study the function and mechanism of signal transduction of signaling（SOCS） in typical myeloproliferative neoplasms（MPNs） patients.Methods By using DNA sequencing detection SOCS1 mutation and methylation specific PCR detection SOCS1 methylation,the real-time PCR was emploied to check SOCS1 expression.Results Methylation of SOCS1 was detected in 37 out of 100（37%） MPNs： 15 out of 44（34%） PV,19 out of 48（38%） ET,3 out of 8（37.5%） MF;Methylation of SOCS1 detected in control groups was 21 out of 173（12%）： 15 out of 93（16%） CML,4 out of 30（13.3%） MDS,2 out of 30（6.7%） AML,0 out of 20 healthy wolunteers.Methylation of SOCS1 greatly inhibited gene expression in MPNs as compared with no SOCS1 methylation（P0.05）.The presence of SOCS1 methylation was found to be significantly at advanced age at the time of diagnosis and with higher leukocyte count than patients with unmethylated.SOCS1 methylation patients were more prone to progress into typical MPN as compared with non-SOCS1 methylation patients.Non-methylation patients were not associated with peripheral blood counts and age.No mutation was found in gene sequencing of SOCS1.Conclusion Methylation of SOCS1 exists in MPNs which inhibits SOCS1 gene expression and the development and metastasis.SOCS1 methylation is related to advanced age,higher leukocyte counts and hemoglobin level in MPNs.SOCS1 hyper-methylation can activate JAK-STAT signaling pathways or accompany JAK2 mutations.These changes may represent a potential therapeutic direction.