title: The role of extracellular histones in haematological disorders.
abstract: 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.
authors.affiliation: Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.
authors.forename: Yasir
authors.initials: Y
authors.lastname: Alhamdi
authors.affiliation: Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.|Roald Dahl Haemostasis & Thrombosis Centre, Royal Liverpool University Hospital, Liverpool, UK.
authors.forename: Cheng-Hock
authors.initials: CH
authors.lastname: Toh
mesh_terms: D001777:Blood Coagulation; D016923:Cell Death; D065206:Extracellular Traps / Q000502:physiology; D006402:Hematologic Diseases / Q000473:pathology / Q000503:physiopathology*; D006657:Histones / Q000097:blood / Q000502:physiology*; D006801:Humans
chemical_list: D006657:Histones
keywords: cell death; extracellular histones; neutrophil extracellular traps; nucleosomes; thrombin