Role of the bone morphogenic protein pathway in developmental haemopoiesis and leukaemogenesis

Toofan, P. and Wheadon, H. (2016) Role of the bone morphogenic protein pathway in developmental haemopoiesis and leukaemogenesis. Biochemical Society Transactions, 44(5), pp. 1455-1463. (doi: 10.1042/BST20160104) (PMID:27911727)

Abstract

Myeloid leukaemias share the common characteristics of being stem cell-derived clonal diseases, characterised by excessive proliferation of one or more myeloid lineage. Chronic myeloid leukaemia (CML) arises from a genetic alteration in a normal haemopoietic stem cell (HSC) giving rise to a leukaemic stem cell (LSC) within the bone marrow (BM) ‘niche’. CML is characterised by the presence of the oncogenic tyrosine kinase fusion protein breakpoint cluster region-abelson murine leukaemia viral oncogene homolog 1 (BCR-ABL), which is responsible for driving the disease through activation of downstream signal transduction pathways. Recent evidence from our group and others indicates that important regulatory networks involved in establishing primitive and definitive haemopoiesis during development are reactivated in myeloid leukaemia, giving rise to an LSC population with altered self-renewal and differentiation properties. In this review, we explore the role the bone morphogenic protein (BMP) signalling plays in stem cell pluripotency, developmental haemopoiesis, HSC maintenance and the implication of altered BMP signalling on LSC persistence in the BM niche. Overall, we emphasise how the BMP and Wnt pathways converge to alter the Cdx–Hox axis and the implications of this in the pathogenesis of myeloid malignancies.

• Item Type: Articles
• Additional Information: This work was supported by a PhD studentship from the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Toofan, Miss Parto and Wheadon, Professor Helen
• Authors: Toofan, P., and Wheadon, H.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Biochemical Society Transactions
• Publisher: Portland Press
• ISSN: 0300-5127
• ISSN (Online): 1470-8752
• Copyright Holders: Copyright © 2016 The Authors
• First Published: First published in Biochemical Society Transactions 44(5): 1455-1463
• Publisher Policy: Reproduced in accordance with the publisher copyright policy