Affiliation:
1. Department of Haematology, Jeffrey Cheah Biomedical Centre University of Cambridge UK
2. Cambridge Stem Cell Institute University of Cambridge UK
3. Haematology Service Cambridge University Hospitals UK
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.
Funder
Cancer Research UK
NIHR Cambridge Biomedical Research Centre
Wellcome Trust
Subject
Cancer Research,Genetics,Molecular Medicine,General Medicine,Oncology