The role of extracellular histones in haematological disorders
The role of extracellular histones in haematological disorders
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DOI：
10.1111/bjh.14077
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发表时间：
2016-06-01
影响因子：
6.5
通讯作者：
Toh, Cheng-Hock
中科院分区：
文献类型：
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作者：
Alhamdi, Yasir;Toh, Cheng-Hock
在过去的几十年中，染色体改变因其在血液恶性肿瘤中的病理生理学相关性而被广泛研究。特别是，核内组蛋白的表观遗传修饰现在被认为是健康细胞周期的关键调节因子，也已演变成某些血癌的新治疗靶点。因此，对于大多数血液学家来说，组蛋白是深埋在染色质内的 DNA 链蛋白质。然而，随着最近关于组蛋白在细胞死亡时解链并释放到细胞外或作为中性粒细胞胞外陷阱（NET）的一部分从激活的中性粒细胞中释放出来的功能的揭示，情节变得更加深入。人们越来越认识到细胞外组蛋白和 NET 具有深远的细胞毒性和促凝血作用。本文强调了认识细胞外组蛋白这种新模式作为宿主防御中关键角色的重要性，其损伤相关分子模式可以转化为各种血液学和危重疾病的新型诊断和治疗生物标志物。
Over the past decades, chromosomal alterations have been extensively investigated for their pathophysiological relevance in haematological malignancies. In particular, epigenetic modifications of intra-nuclear histones are now known as key regulators of healthy cell cycles that have also evolved into novel therapeutic targets for certain blood cancers. Thus, for most haematologists, histones are DNA-chained proteins that are buried deep within chromatin. However, the plot has deepened with recent revelations on the function of histones when unchained and released extracellularly upon cell death or from activated neutrophils as part of neutrophil extracellular traps (NETs). Extracellular histones and NETs are increasingly recognized for profound cytotoxicity and pro-coagulant effects. This article highlights the importance of recognizing this new paradigm of extracellular histones as a key player in host defence through its damage-associated molecular patterns, which could translate into novel diagnostic and therapeutic biomarkers in various haematological and critical disorders.