title: Role of the bone morphogenic protein pathway in developmental haemopoiesis and leukaemogenesis.
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.
authors.affiliation: 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.
authors.forename: Parto
authors.initials: P
authors.lastname: Toofan
authors.affiliation: 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.
authors.forename: Helen
authors.initials: H
authors.lastname: Wheadon
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D063646:Carcinogenesis / Q000378:metabolism; D006410:Hematopoiesis; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism* / Q000503:physiopathology; D008954:Models, Biological; D014411:Neoplastic Stem Cells / Q000378:metabolism; D015398:Signal Transduction; D055153:Stem Cell Niche
chemical_list: D019485:Bone Morphogenetic Proteins
keywords: Cdx–Hox; bone marrow (BM) niche; bone morphogenic protein (BMP) pathway; chronic myeloid leukaemia (CML); haemopoiesis; leukaemic stem cell (LSC)