• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文学位 >Progressive chromatin repression and promoter methylation of CTNNA1 associated with advanced myeloid malignancies.
【24h】

Progressive chromatin repression and promoter methylation of CTNNA1 associated with advanced myeloid malignancies.

机译：CTNNA1的渐进性染色质抑制和启动子甲基化与晚期髓样恶性肿瘤相关。

获取原文
获取原文并翻译 | 示例
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Complete loss or deletion of the long arm of chromosome 5 is frequent in myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). The putative gene(s) deleted and responsible for the pathogenesis of these poor prognosis hematological disorders remain controversial. This study represents a comprehensive analysis of previously implicated and novel genes on 5q, exploring epigenetic inactivation of some genes in that region in AML and MDS. Through an examination of 146 AML cases, DNA methylation of CTNNA1 was discovered to be frequent, and more common in AML patients with 5q deletion (31%) than those without 5q deletion (14%), while no inactivation of other 5q genes was observed. In 31 MDS cases, CTNNA1 methylation was only found in high risk MDS (≥2AEB2), but not in low risk MDS (RAEB2), suggesting that CTNNA1 methylation is important in the transformation of MDS to AML. CTNNA1 expression was lowest in AML/MDS patients with CTNNA1 methylation, although reduced expression occurred in some patients without promoter methylation. Repressive chromatin marks (H3K27me3) at the promoter were identified in CTNNA1-repressed AML cell lines and primary leukemias, with the most repressive state correlating with DNA methylation. We observed DNMT1 occupancy of the CTNNA1 promoter in a leukemia cell line with silenced and methylated CTNNA1, and also in cell lines with repressed, but unmethylated CTNNA1, where DNMT1 enrichment directly correlates with the level of CTNNA1 repression. This suggests that DNMT1 plays a critical role in initiating and/or maintaining DNA repression of CTNNA1 in AML cell lines, which is also consistent with the observed increase in expression of CTNNA1 following treatment with 5-aza-dC, a drug that depletes DNMT1 and thus reduces DNA methylation in dividing cells. Our study demonstrates progressive, acquired epigenetic inactivation at CTNNA1, including histone modifications and promoter CpG methylation, as a component of leukemia progression in patients with both 5q- and non 5q-myeloid malignancies.
机译：在骨髓增生异常综合症（MDS）和急性骨髓性白血病（AML）中，5号染色体长臂的完全丢失或缺失是很常见的。推测的基因缺失并导致这些不良预后的血液学疾病的发病机理仍然存在争议。这项研究代表了对5q上先前涉及的新基因的全面分析，探讨了AML和MDS中该区域某些基因的表观遗传失活。通过检查146例AML病例，发现CTNNA1的DNA甲基化很常见，在缺失5q的AML患者中（31％）比未缺失5q的AML患者（14％）更常见，而未观察到其他5q基因的失活。在31例MDS病例中，仅在高危MDS（≥2AEB2）中发现CTNNA1甲基化，而在低危MDS（

著录项

  • 作者

    Ye, Ying.;

  • 作者单位

    The Johns Hopkins University.;

  • 授予单位 The Johns Hopkins University.;
  • 学科 Biology Molecular.;Health Sciences Pathology.
  • 学位 Ph.D.
  • 年度 2010
  • 页码 107 p.
  • 总页数 107
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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