中文摘要：

目的：探讨细胞信号转导抑制因子1（suppressor of cytokine signaling1,SOCS1）基因超甲基化在经典型慢性骨髓增殖性肿瘤（myelo-proliferative neoplasms,MPNs）中的临床作用及其机制。方法：采用甲基化特异性PCR法检测MPNs患者骨髓标本中SOCS1基因的超甲基化发生情况。应用粒细胞集落刺激因子（granulocyte colony stimulating factor,G-CSF）化学诱导MPNs细胞生长不同时间后,实时定量PCR和蛋白质印迹法检测SOCS1mRNA及其蛋白表达情况。另外,加入去甲基化试剂2-deoxyazacytidin培养MPNs细胞不同时间后,实时定量PCR法检测SOCS1mRNA表达情况。结果：100例经典型慢性MPNs患者中有27例（27.0%）存在SOCS1基因超甲基化。G-CSF化学诱导处理后的MPNs细胞中,SOCS1基因超甲基化组与未甲基化组相比,其SOCS1mRNA表达量均明显减少（均P〈0.05）;MPNs患者中SOCS1基因超甲基化组的SOCS1蛋白表达量也减少,但与健康对照组相比差异尚无统计学意义（P〉0.05）。另外,相对于G-CSF处理后的超甲基化组,加入去甲基化试剂后SOCS1mRNA表达量明显升高（P〈0.05）。结论：MPNs患者中存在SOCS1基因超甲基化,且CpG岛超甲基化导致其基因表达水平降低,去甲基化后,其基因表达水平升高。提示SOCS1基因超甲基化可能和MPNs发病有关,去甲基化可能是一种潜在的治疗MPNs的新策略。

英文摘要：

Objective： To investigate the clinical significance of suppressor of cytokine signaling 1 （SOCS1） hypermethylation in typical myelo-proliferative neoplasms （MPNs）, and to discuss the potential mechanism. Methods： Methylation specific PCR was used to detect the hypermethylation status of SOCS1 gene in bone marrow specimens from patients with typical MPNs. Granulocyte colony stimulating factor （G-CSF） was used as a chemical inducer to simulate the MPNs cells for different time, then the real-time quantitative PCR and Western blotting were applied to evaluate the expressions of SOCS1 mRNA and protein, respectively. After the demethylating agent 2-deoxyazacytidin was used to cultivate MPNs cells for different time, SOCS1 mRNA expression was detected by real-time quantitative PCR. Results： Hypermethylation of SOCS1 was detected in 27 of 100 （27.0%） cases of MPNs. The expressions of SOCS1 mRNA in the MPNs cells were significantly decreased after G-CSF intervention in the SOCS1 hypermethylation groups as compared with those in the non-methylation groups （P0.05）. The expressions of SOCS1 protein in the SOCS1 hypermethylation groups from patients with MPNs were decreased, but there was no statistically significant difference as compared with normal controls （P0.05）. In addition, SOCS1 mRNA expression was markedly promoted in MPNs cells after treatment with the demethylating agent as compared with the hypermethylated groups induced by G-CSF The roles of hypermethylation and demethylation of suppressor of cytokine signaling 1 gene in typical myelo-proliferative neoplasms QIN Wei, LU Hui-na, HUANG Bin-bin, XIU Bing, BO Lan-jun, GAO Qing-mei, ZHANG Wen-jun, LIANG Ai-bin Department of Hematology, Tongji Hospital, Tongji University, Shanghai 200065, China Abstract Objective： To investigate the clinical significance of suppressor of cytokine signaling 1 （SOCS1） hypermethylation in typical myelo-proliferative neoplasms （MPNs）, and to discuss the potential mechanism. Methods： Methylation s