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多发性骨髓瘤中的表观遗传修饰:DNA和组蛋白甲基化作用的最新进展

Epigenetic modifications in multiple myeloma: recent advances on the role of DNA and histone methylation.

作者信息

Amodio Nicola, D'Aquila Patrizia, Passarino Giuseppe, Tassone Pierfrancesco, Bellizzi Dina

机构信息

a Department of Experimental and Clinical Medicine , Magna Graecia University , Catanzaro , Italy.

b Department of Biology, Ecology and Earth Sciences , University of Calabria , Rende , Italy.

出版信息

Expert Opin Ther Targets. 2017 Jan;21(1):91-101. doi: 10.1080/14728222.2016.1266339.

Abstract

Multiple Myeloma (MM) is a clonal late B-cell disorder accounting for about 13% of hematological cancers and 1% of all neoplastic diseases. Recent studies on the molecular pathogenesis and biology of MM have highlighted a complex epigenomic landscape contributing to MM onset, prognosis and high individual variability. Areas covered: We describe here the current knowledge on epigenetic events characterizing MM initiation and progression, focusing on the role of DNA and histone methylation and on the most promising epi-therapeutic approaches targeting the methylation pathway. Expert opinion: Data published so far indicate that alterations of the epigenetic framework, which include aberrant global or gene/non-coding RNA specific methylation profiles, feature prominently in the pathobiology of MM. Indeed, the aberrant expression of components of the epigenetic machinery as well as the reversibility of the epigenetic marks make this pathway druggable, providing the basis for the design of epigenetic therapies against this still fatal malignancy.

摘要

多发性骨髓瘤(MM)是一种克隆性晚期B细胞疾病,约占血液系统癌症的13%,占所有肿瘤性疾病的1%。最近关于MM分子发病机制和生物学的研究突出了一个复杂的表观基因组格局,这一格局与MM的发病、预后及高度的个体变异性有关。涵盖领域:我们在此描述目前关于MM起始和进展特征性表观遗传事件的知识,重点关注DNA和组蛋白甲基化的作用以及针对甲基化途径最有前景的表观治疗方法。专家观点:迄今为止发表的数据表明,表观遗传框架的改变,包括异常的整体或基因/非编码RNA特异性甲基化谱,在MM的病理生物学中显著存在。事实上,表观遗传机制成分的异常表达以及表观遗传标记的可逆性使该途径具有可药物靶向性,为针对这种仍然致命的恶性肿瘤设计表观遗传疗法提供了基础。

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