Clonality in haematopoietic stem cell ageing

Terradas-Terradas, M. , Robertson, N. A., Chandra, T. and Kirschner, K. (2020) Clonality in haematopoietic stem cell ageing. Mechanisms of Ageing and Development, 189, 111279. (doi: 10.1016/j.mad.2020.111279) (PMID:32526214) (PMCID:PMC7347006)

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Abstract

Clonal haematopoiesis of indeterminate potential (CHIP) is widespread in the elderly. CHIP is driven by somatic mutations in leukaemia driver genes, such as Janus Kinase 2 (JAK2), Tet methylcytosine dioxygenase 2 (TET2), ASXL Transcriptional Regulator 1 (ASXL1) and DNA (cytosine-5)-methyltransferase 3A (DNMT3A), leading to reduced diversity of the blood pool. CHIP carries an increased risk for leukaemia and cardiovascular disease. Apart from mutations driving CHIP, environmental factors such as chemokines and cytokines have been implicated in age-dependent multimorbidities associated with CHIP. However, the mechanism of CHIP onset and the relationship with environmental and cell-intrinsic factors remain poorly understood. Here we contrast cell-intrinsic and environmental factors involved in CHIP development and disease propagation.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Terradas Terradas, Maria and Kirschner, Dr Kristina and Robertson, Mr Neil
Authors: Terradas-Terradas, M., Robertson, N. A., Chandra, T., and Kirschner, K.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Mechanisms of Ageing and Development
Publisher:Elsevier
ISSN:0047-6374
ISSN (Online):1872-6216
Published Online:08 June 2020
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in Mechanisms of Ageing and Development 189: 111279
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
306709Early detection of pre-leukaemic clones in the aged haematopoietic compartment using single cell approachesKristina KirschnerLeuka (LEUKA)2019/JGF/003CS - Epigenetics
304005MRC Precision Medicine Training GrantMorven BarlassMedical Research Council (MRC)MR/N013166/1-LGH/MS/MED25CAMS - Cardiovascular Science