Key roles of histone methyltransferase and demethylase in leukemogenesis
Key roles of histone methyltransferase and demethylase in leukemogenesis
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DOI：
10.1002/jcb.22972
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发表时间：
2011-02
影响因子：
4
通讯作者：
A. Yoshimi;M. Kurokawa
中科院分区：
文献类型：
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作者：
A. Yoshimi;M. Kurokawa
越来越多的证据表明组蛋白甲基转移酶和脱甲基酶参与白血病的发生。这些发现可以根据它们与白血病的关系大致分为两类。一方面，这些组蛋白修饰剂通过异常表达的转录因子或融合蛋白的特异性亲和力被募集到DNA中，并诱导染色质修饰以调节靶基因的表达。在这种情况下，表观遗传调节因子可能起癌基因的作用。另一方面，最近的研究已经确定了髓系恶性肿瘤中一些关键组蛋白调节剂的失活突变，这些结果表明它们作为肿瘤抑制剂。深入了解这两类研究结果将有助于我们考虑表观遗传药物的临床应用。在这个前景中，我们将回顾白血病的发生机制澄清的表观遗传学的方法和目前的研究结果，遗传畸变在每个甲基转移酶或脱甲基酶，并讨论潜在的医疗干预白血病或白血病干细胞靶向组蛋白修饰。J.细胞。112：415-424，2011.© 2010 Wiley利斯公司
A growing body of evidence has underlined the involvement of histone methyltransferases and demethylases in leukemia development. These findings can be roughly classified into two categories according to their association with leukemia. On the one hand, these histone modifiers are recruited to DNA by specific affinities of aberrantly expressed transcription factors or fusion proteins, and induce chromatin modifications to regulate target gene expression. Epigenetic regulators may function as oncogenes in this context. On the other hand, recent studies have identified inactivating mutations of some key histone modulators in myeloid malignancies and these results suggest that they act as tumor suppressors. Profound understanding of these findings in the two categories will help us consider clinical applications of epigenetic drugs. In this prospect we will review the leukemogenic mechanisms clarified by the epigenetic approach and the current findings on genetic aberrations in each methyltransferase or demethylase, and discuss the potential of medical intervention in leukemia or leukemia stem cells targeting histone modifiers. J. Cell. Biochem. 112: 415–424, 2011. © 2010 Wiley‐Liss, Inc.