title: Targeting self-renewal pathways in myeloid malignancies.
abstract: A fundamental property of hematopoietic stem cells (HSCs) is the ability to self-renew. This is a complex process involving multiple signal transduction cascades which control the fine balance between self-renewal and differentiation through transcriptional networks. Key activators/regulators of self-renewal include chemokines, cytokines and morphogens which are expressed in the bone marrow niche, either in a paracrine or autocrine fashion, and modulate stem cell behaviour. Increasing evidence suggests that the downstream signaling pathways induced by these ligands converge at multiple levels providing a degree of redundancy in steady state hematopoiesis. Here we will focus on how these pathways cross-talk to regulate HSC self-renewal highlighting potential therapeutic windows which could be targeted to prevent leukemic stem cell self-renewal in myeloid malignancies.
authors.affiliation: Paul O'Gorman Leukaemia Research Centre, College of Medical, Veterinary and Life Sciences, University of Glasgow, Gartnavel General Hospital, 1053 Great Western Road, Glasgow G12 0ZD, UK. Helen.Wheadon@glasgow.ac.uk.
authors.forename: William A
authors.initials: WA
authors.lastname: Sands
authors.forename: Mhairi
authors.initials: M
authors.lastname: Copland
authors.forename: Helen
authors.initials: H
authors.lastname: Wheadon