...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Oncogene >Differential methylation of genes that regulate cytokine signaling in lymphoid and hematopoietic tumors
【24h】

Differential methylation of genes that regulate cytokine signaling in lymphoid and hematopoietic tumors

机译：调节淋巴样和造血肿瘤细胞因子信号传导的基因的差异甲基化

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The perturbations of the cytokine signaling pathway play an important role in lymphoid/hematopoietic tumors. Aberrant promoter methylation is the major mechanism of gene silencing in tumors. We examined 150 lymphoid/hematopoietic tumors or potential premalignant specimens, 55 control specimens and 12 EBV-transformed B lymphoblastoid cultures and 10 lymphoma/leukemia (L/L) or multiple myeloma (MM) cell lines for the methylation (and, in cell lines, of the expression status) of three genes involved in the cytokine signaling pathway. The genes were: SHP1, a protein tyrosine phosphatase; SYK, a protein kinase; and SOCS1, a suppressor of cytokine signaling. Our major findings were: (1) one or more of the three genes was frequently methylated in L/L and MM cell lines and there was good concordance (90–100%) between methylation and loss of gene expression; (2) treatment of L/L cell lines with a demethylating agent resulted in re-expression of SHP1 protein and downregulation of phosphorylated STAT3 in L/L cell lines; (3) all 55 control specimens and the lymphoblastoid cultures were negative for methylation of the three genes; (4) non-Hodgkin's lymphomas (100%), and leukemias (94%) had almost universal methylation of SHP1 and relatively less frequent (SOCS1 and SYK; (5) MM and monoclonal gammopathy of unknown significance (MGUS) had infrequent methylation of SHP1 (SOCS1 and SYK; and (6) comparable methylation frequencies for SOCS1 were observed in MM and MGUS, suggesting that SOCS1 methylation is an early event in MM pathogenesis. At least one gene was methylated in 119 of 130 (93%) of the malignant and 12 of 20 (60%) of the MGUS samples. Our findings demonstrate that the perturbations of cytokine signaling via silencing of these three genes are almost universal in lymphoid/hematopoietic tumors but the patterns of gene methylated for L/L and plasma cell dyscrasias are different.
机译：细胞因子信号通路的扰动在淋巴样/造血性肿瘤中起重要作用。启动子异常甲基化是肿瘤中基因沉默的主要机制。我们检查了150个淋巴样/造血性肿瘤或潜在的恶性前标本，55个对照标本和12个EBV转化的B淋巴母细胞培养物和10个淋巴瘤/白血病（L / L）或多发性骨髓瘤（MM）细胞系的甲基化程度（以及在细胞系中（涉及表达状态），这三个参与细胞因子信号传导途径的基因。基因是：SHP1，一种蛋白质酪氨酸磷酸酶; SYK，一种蛋白激酶; SOCS1，一种细胞因子信号转导的抑制剂。我们的主要发现是：（1）三个基因中的一个或多个在L / L和MM细胞系中经常被甲基化，并且甲基化和基因表达丧失之间有很好的一致性（90-100％）; （2）用去甲基化剂处理L / L细胞系导致SHP1蛋白的重新表达和L / L细胞系中磷酸化STAT3的下调; （3）所有55个对照标本和淋巴母细胞培养物三个基因的甲基化均为阴性; （4）非霍奇金淋巴瘤（100％）和白血病（94％）具有几乎普遍的SHP1甲基化并且相对较少发生（SOCS1和SYK）;（5）MM和未知意义的单克隆丙种球蛋白病（MGUS）很少在MM和MGUS中观察到SHP1的甲基化（SOCS1和SYK;（6）SOCS1的甲基化频率相当，这表明SOCS1甲基化是MM发病的早期事件，至少有一个基因在130的119中被甲基化（93 ％ ）和MGUS样品中的20个（60％）中的12个（我们的发现表明，通过沉默这三个基因引起的细胞因子信号的扰动在淋巴样/造血性肿瘤中几乎普遍存在，但L / L和浆细胞性痢疾有所不同。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号