急性髓系白血病中转录因子C/EBPα的异常DNA甲基化
Aberrant DNA methylation of the transcription factor C/EBPalpha in acute myelogenous leukemia.
作者信息
Jost Edgar, do O Nicole, Wilop Stefan, Herman James G, Osieka Rainhardt, Galm Oliver
机构信息
Medizinische Klinik IV, Universitaetsklinikum Aachen, RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany.
出版信息
Leuk Res. 2009 Mar;33(3):443-9. doi: 10.1016/j.leukres.2008.07.027. Epub 2008 Aug 30.
We investigated the methylation status of the CCAAT/enhancer binding protein alpha (C/EBPalpha) promoter region near the transcription start site in acute myelogenous leukemia (AML). In hematopoietic tumor cell lines, CpG island hypermethylation of the proximal C/EBPalpha promoter region was associated with transcriptional silencing, and treatment with the demethylating agent 5-aza-2'-deoxycytidine resulted in C/EBPalpha reexpression and promoter demethylation. Aberrant methylation of the C/EBPalpha promoter region occurred in 10/80 diagnostic AML samples, and there was an inverse correlation between aberrant methylation of C/EBPalpha and the negative cell cycle regulator p15. Our results provide further evidence for epigenetic dysregulation of C/EBPalpha in AML.
我们研究了急性髓性白血病（AML）中转录起始位点附近CCAAT/增强子结合蛋白α（C/EBPα）启动子区域的甲基化状态。在造血肿瘤细胞系中，近端C/EBPα启动子区域的CpG岛高甲基化与转录沉默相关，用去甲基化剂5-氮杂-2'-脱氧胞苷处理导致C/EBPα重新表达和启动子去甲基化。在80例诊断为AML的样本中，有10例发生了C/EBPα启动子区域的异常甲基化，且C/EBPα的异常甲基化与负性细胞周期调节因子p15之间呈负相关。我们的结果为AML中C/EBPα的表观遗传失调提供了进一步的证据。
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