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A guide to epigenetics in leukaemia stem cells.

Published version
Peer-reviewed

Repository DOI


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Authors

Agrawal-Singh, Shuchi  ORCID logo  https://orcid.org/0000-0001-8632-4556
Bagri, Jaana 
Sakakini, Nathalie 

Abstract

Leukaemia stem cells (LSCs) are the critical seed for the growth of haematological malignancies, driving the clonal expansion that enables disease initiation, relapse and often resistance. Specifically, they display inherent phenotypic and epigenetic plasticity resulting in complex heterogenic diseases. In this review, we discuss the key principles of deregulation of epigenetic processes that shape this disease evolution. We consider measures to define and quantify clonal heterogeneity, combining information from recent studies assessing mutational, transcriptional and epigenetic landscapes at single cell resolution in myeloid neoplasms (MN). We highlight the importance of integrating epigenetic and genetic information to better understand inter- and intra-patient heterogeneity and discuss how this understanding further informs evolution and progression trajectories and subsequent clinical response in MN. Under this topic, we also discuss efforts to identify mechanisms of resistance, by longitudinal analyses of patient samples. Finally, we highlight how we might target these aberrant epigenetic processes for better therapeutic outcomes and to potentially eradicate LSCs.

Description

Publication status: Published

Keywords

epigenetic plasticity, heterogeneity, leukaemia stem cells, myeloid neoplasms, single cell studies and multiomics, targeting LSC, Humans, Leukemia, Myeloid, Acute, Epigenesis, Genetic, Mutation, Stem Cells, Neoplastic Stem Cells

Journal Title

Mol Oncol

Conference Name

Journal ISSN

1574-7891
1878-0261

Volume Title

Publisher

Wiley
Sponsorship
Cancer Research UK (A25117)
Wellcome Trust (203151/Z/16/Z)
Wellcome Trust (218481/Z/19/Z)
National Institute for Health and Care Research (IS-BRC-1215-20014)
Medical Research Council (MC_PC_17230)