Bone marrow niche crosses paths with BMPs: a road to protection and persistence in CML

Wheadon, H. and Busch, C. (2019) Bone marrow niche crosses paths with BMPs: a road to protection and persistence in CML. Biochemical Society Transactions, 47(5), pp. 1307-1325. (doi: 10.1042/BST20190221) (PMID:31551354)

[img] Text
195426.pdf - Accepted Version

1MB

Abstract

Chronic myeloid leukaemia (CML) is a paradigm of precision medicine, being one of the first cancers to be treated with targeted therapy. This has revolutionised CML therapy and patient outcome, with high survival rates. However, this now means an ever-increasing number of patients are living with the disease on life-long tyrosine kinase inhibitor (TKI) therapy, with most patients anticipated to have near normal life expectancy. Unfortunately, in a significant number of patients, TKIs are not curative. This low-level disease persistence suggests that despite a molecularly targeted therapeutic approach, there are BCR-ABL1-independent mechanisms exploited to sustain the survival of a small cell population of leukaemic stem cells (LSCs). In CML, LSCs display many features akin to haemopoietic stem cells, namely quiescence, self-renewal and the ability to produce mature progeny, this all occurs through intrinsic and extrinsic signals within the specialised microenvironment of the bone marrow (BM) niche. One important avenue of investigation in CML is how the disease highjacks the BM, thereby remodelling this microenvironment to create a niche, which enables LSC persistence and resistance to TKI treatment. In this review, we explore how changes in growth factor levels, in particular, the bone morphogenetic proteins (BMPs) and pro-inflammatory cytokines, impact on cell behaviour, extracellular matrix deposition and bone remodelling in CML. We also discuss the challenges in targeting LSCs and the potential of dual targeting using combination therapies against BMP receptors and BCR-ABL1.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Wheadon, Professor Helen and Busch, Caroline
Authors: Wheadon, H., and Busch, C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Biochemical Society Transactions
Publisher:Portland Press
ISSN:0300-5127
ISSN (Online):1470-8752
Published Online:24 September 2019
Copyright Holders:Copyright © 2019 The Author(s)
First Published:First published in Biochemical Society Transactions 47(5):1307-1325
Publisher Policy:Reproduced in accordance with the publisher copyright policy

University Staff: Request a correction | Enlighten Editors: Update this record