Epigenetic reprogramming and emerging epigenetic therapies in CML

Bugler, J., Kinstrie, R., Scott, M. T. and Vetrie, D. (2019) Epigenetic reprogramming and emerging epigenetic therapies in CML. Frontiers in Cell and Developmental Biology, 7, 136. (doi: 10.3389/fcell.2019.00136) (PMID:31380371) (PMCID:PMC6652210)

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Chronic myeloid leukemia (CML) is a hematopoietic stem cell disorder characterized by BCR-ABL1, an oncogenic fusion gene arising from the Philadelphia chromosome. The development of tyrosine kinase inhibitors (TKIs) to overcome the constitutive tyrosine kinase activity of the BCR-ABL protein has dramatically improved disease management and patient outcomes over the past 20 years. However, the majority of patients are not cured and developing novel therapeutic strategies that target epigenetic processes are a promising avenue to improve cure rates. A number of epigenetic mechanisms are altered or reprogrammed during the development and progression of CML, resulting in alterations in histone modifications, DNA methylation and dysregulation of the transcriptional machinery. In this review these epigenetic alterations are examined and the potential of epigenetic therapies are discussed as a means of eradicating residual disease and offering a potential cure for CML in combination with current therapies.

Item Type:Articles
Keywords:Cell and developmental biology, chronic myeloid leukemia, epigenetics, stem cells, therapies, drug resistance.
Glasgow Author(s) Enlighten ID:Scott, Dr Mary and Kinstrie, Dr Ross and Vetrie, Professor David and Bugler, Ms Jane
Authors: Bugler, J., Kinstrie, R., Scott, M. T., and Vetrie, D.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Frontiers in Cell and Developmental Biology
Publisher:Frontiers Media
ISSN (Online):2296-634X
Copyright Holders:Copyright © 2019 Bugler, Kinstrie, Scott and Vetrie
First Published:First published in Frontiers in Cell and Developmental Biology 7:136
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
171130Crosstalk between PRC2 and BCL6 in regulating CML stem cell survival - from epigenomics to novel therapeutics approachesDavid VetrieBloodwise (BLOODWIS)14047CS - Epigenetics
171051Targeting p53, cMyc and PRC2 regulatory hubs: A systematic and stratified approach to deliver new therapeutics for CMLDavid VetrieBloodwise (BLOODWIS)14033CS - Paul O'Gorman Leukaemia Research Centre
169897Modulation of H3K27 methylation to eradicate TKI-persistant CML stem cellsDavid VetrieBloodwise (BLOODWIS)14005CS - Epigenetics
301129TASTER (TArgeting STEm cell Resistance) - Defining leukaemic cell clonal architecture to inform and monitor drug responses in the TASTER CML Phase II Clinical TrialMhairi CoplandCancer Research UK (CRUK)C55731/A24896CS - Paul O'Gorman Leukaemia Research Centre