Abstract
Epigenetics is the study that involves understanding of the DNA sequence-independent mechanism of transcriptional regulation. The epigenetic regulation of gene expression is exerted via the alteration of chromatin structures through covalent modifications of core histone tails and methylation of CpG dinucleotides. In general, histone acetylation and DNA methylation are associated with transcriptional activation and repression, respectively. Histone methylation offers an additional layer for transcriptional regulation. Epigenetic abnormalities underlie the development of various hematological malignancies; for example, recurrent mutations of the DNA methyltransferase DNMT3A or DNA demethylase TET2 transform hematopoietic stem cells into preleukemic stem cells. Consequently, preleukemic stem cells give rise to T-cell lymphomas, such as angioimmunoblastic T-cell lymphoma and T-cell lymphoblastic lymphoma. Epigenetic alterations could be ideal therapeutic targets; indeed, HDAC inhibitors and DNA demethylating agents have already been used for the treatment of peripheral T-cell lymphomas. It is anticipated that more number of epigenetic drugs would be developed for clinical application in the near future.
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Schedule a callMore From: [Rinsho ketsueki] The Japanese journal of clinical hematology
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