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.
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October 2016
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Cover Image
Alternative splicing of intrinsically disordered segments can rewire protein interaction networks. In this issue, the Biochemical Society’s Colworth Medal winner, M. Madan Babu explores the contribution of intrinsically disordered regions to protein function, cellular complexity and human disease; see pages 1185–1200. [Credit: Guilhem Chalancon, MRC Laboratory of Molecular Biology, Cambridge, UK.]
Review Article|
October 19 2016
Role of the bone morphogenic protein pathway in developmental haemopoiesis and leukaemogenesis
Parto Toofan;
Parto Toofan
Paul O'Gorman Leukaemia Research Centre, College of Medical, Veterinary and Life Sciences, University of Glasgow, 1053 Great Western Road, Glasgow G12 0XB, U.K.
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Helen Wheadon
Helen Wheadon
Paul O'Gorman Leukaemia Research Centre, College of Medical, Veterinary and Life Sciences, University of Glasgow, 1053 Great Western Road, Glasgow G12 0XB, U.K.
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Publisher: Portland Press Ltd
Received:
April 08 2016
Revision Received:
June 23 2016
Accepted:
June 27 2016
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society
2016
Biochem Soc Trans (2016) 44 (5): 1455–1463.
Article history
Received:
April 08 2016
Revision Received:
June 23 2016
Accepted:
June 27 2016
Citation
Parto Toofan, Helen Wheadon; Role of the bone morphogenic protein pathway in developmental haemopoiesis and leukaemogenesis. Biochem Soc Trans 15 October 2016; 44 (5): 1455–1463. doi: https://doi.org/10.1042/BST20160104
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