Qin Wei, Li Ling-li, Lu Hui-na, Huang Bin-bin, Xiu Bing, Bo Lan-jun, Gao Qing-mei, Zhang Wen-jun, Fu Jian-fei
Department of Hematology, Tongji Hospital, Tongji University, Shanghai, China.
Zhonghua Xue Ye Xue Za Zhi. 2011 Nov;32(11):772-6.
To investigate the clinical role of hypermethylation of suppressor of cytokine signaling (SOCS) on typical myeloproliferative disease (MPD) patients and its mechanism.
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.
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).
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.
探讨细胞因子信号转导抑制因子（SOCS）甲基化在典型骨髓增殖性疾病（MPD）患者中的临床作用及其机制。
采用甲基化特异性PCR检测SOCS1、2、3甲基化，直接DNA测序检测JAK2V617F突变，实时荧光定量PCR评估SOCS1、2、3转录活性。
100例MPD患者中，27例（27%）检测到SOCS1甲基化，9例（9%）检测到SOCS2甲基化，34例（34%）检测到SOCS3甲基化；64例（64%）检测到JAK2V617F突变。与未甲基化相比，SOCS1、3甲基化显著抑制基因表达（P<0.05）。与野生型JAK2V617F相比，JAK2V617F突变的存在显著下调SOCS1、3基因mRNA表达（P<0.05）。
MPD患者存在SOCS1、3甲基化及JAK2V617F突变，抑制了SOCS1、3基因表达。SOCS甲基化和JAK2V617F突变可激活JAK-STAT信号通路，这些观察结果可能提供一个潜在的治疗方向。
