文章：

组蛋白修饰物在多发性骨髓瘤中的生物学意义：临床应用

The biological significance of histone modifiers in multiple myeloma: clinical applications

原文发布日期：2018-08-22

DOI: 10.1038/s41408-018-0119-y

类型: Review Article

开放获取: 是

英文摘要：

Multiple myeloma (MM) is a clonal plasma cell disorder that is characterized by a variety of genetic alterations. Recent studies have highlighted not only the importance of these genetic events but also epigenetic aberrations including DNA methylation, histone modifications, and non-coding RNAs in the biology of MM. Post-translational modifications of histone, such as methylation and acetylation, contribute to chromatin dynamics, and are modulated by histone modifying enzymes, and dysregulation of these enzymes is implicated in the pathogenesis of cancers, including MM. Histone modifiers also have non-histone substrates and enzymatically independent roles, which are also involved in tumorigenesis. Here we review and provide comprehensive insight into the biologic significance of histone methyl- and acetyl-modifiers in MM, and further provide an overview of the clinical applications of histone modifier inhibitors, especially histone deacetylase inhibitors. These findings underline the emerging roles of histone modifiers in the pathogenesis of MM, and further highlight the possibility of novel epigenetic therapies in MM.

摘要翻译： 

多发性骨髓瘤（MM）是一种以多种遗传学改变为特征的克隆性浆细胞疾病。近期研究不仅揭示了遗传学事件的重要性，更强调了表观遗传学异常（包括DNA甲基化、组蛋白修饰和非编码RNA）在MM生物学中的重要作用。组蛋白的翻译后修饰（如甲基化与乙酰化）参与染色质动态调控，受组蛋白修饰酶调节，这些酶的失调与MM在内的多种肿瘤发病机制相关。组蛋白修饰酶还具有非组蛋白底物和非酶功能性作用，这些功能也参与肿瘤发生过程。本文系统回顾并全面阐述了组蛋白甲基化/乙酰化修饰酶在MM中的生物学意义，进一步概述了组蛋白修饰酶抑制剂（尤其是组蛋白去乙酰化酶抑制剂）的临床应用。这些研究发现揭示了组蛋白修饰酶在MM发病机制中的新兴作用，并进一步凸显了表观遗传靶向疗法在MM治疗中的潜力。

原文链接：

The biological significance of histone modifiers in multiple myeloma: clinical applications