Section of Experimental Haematology, Leeds Institute of Molecular Medicine, St James's University Hospital, University of Leeds, Leeds, LS97TF, UK.
Expert Rev Mol Med. 2010 Feb 15;12:e6. doi: 10.1017/S1462399410001377.
It is now well established that epigenetic phenomena and aberrant gene regulation play a major role in carcinogenesis. These include aberrant gene silencing by imposing inactive histone marks on promoters, aberrant methylation of DNA at CpG islands, and the active repression of promoters by oncoproteins. In addition, many malignant cells also show aberrant gene activation due to constitutively active signalling. The next frontier in cancer research will be to examine how, at the molecular level, small mutations that alter the regulatory phenotype of a cell give rise after a number of cell divisions to the vast deregulation phenomena seen in malignant cells. This review outlines recent insights into how normal cell differentiation in the haematopoietic system is subverted in leukaemia and it introduces the molecular players involved in this process. It also summarises the results of recent clinical trials trying to reverse aberrant epigenetic regulation by employing agents influencing global epigenetic regulators.
现在已经明确，表观遗传现象和异常基因调控在癌症发生中起着重要作用。这些现象包括通过在启动子上施加无活性组蛋白标记来使异常基因沉默、CpG 岛上的 DNA 异常甲基化，以及致癌蛋白对启动子的主动抑制。此外，许多恶性细胞还由于持续激活的信号而表现出异常基因激活。癌症研究的下一个前沿领域将是研究在分子水平上，改变细胞调控表型的微小突变如何在经过多次细胞分裂后，导致恶性细胞中出现广泛的失调现象。这篇综述概述了最近在了解造血系统中正常细胞分化如何在白血病中被颠覆方面的进展，并介绍了参与这一过程的分子机制。它还总结了最近试图通过使用影响全局表观遗传调控因子的药物来逆转异常表观遗传调控的临床试验结果。
