title: Stem Cell Guardians - Old and New Perspectives in LSC Biology.
abstract: The introduction of tyrosine kinase inhibitors in chronic myeloid leukaemia (CML) has revolutionised disease outcome. However, despite this, progression to blast phase disease is high in those that do not achieve complete cytogenetic and major molecular response on standard therapy. As well as BCR-ABL-dependent mechanisms, disease persistence has been shown to play a key role. Disease persistence suggests that, despite a targeted therapeutic approach, BCR-ABL-independent mechanisms are being exploited to sustain the survival of a small population of cells termed leukaemic stem cells (LSCs). Increasing evidence highlights the importance of self-renewal and survival pathways in this process. This review will focus on the role of stem-cell restricted self-renewal pathways, namely Hedgehog, Notch, and Bone Morphogenic Pathway (BMP). Wingless-Int/β-Catenin (Wnt/β-Catenin) signalling will be discussed within a further review in this series in view of its regulatory role in GSK3β. Further to this, we will highlight the role of key transcriptional regulators, namely p53 and c- MYC, in targeting wider deregulated networks.
authors.affiliation: Wellcome Trust Research Training Fellow, Paul O'Gorman Leukaemia Research Centre, College of Medical, Veterinary & Life Sciences, Institute of Cancer Sciences, University of Glasgow, Gartnavel General Hospital 21 Shelley Road, Glasgow, G12 OXB, United Kingdom.
authors.forename: Gillian A
authors.initials: GA
authors.lastname: Horne
authors.forename: Lorna
authors.initials: L
authors.lastname: Jackson
authors.forename: Vignir
authors.initials: V
authors.lastname: Helgason
authors.forename: Tessa L
authors.initials: TL
authors.lastname: Holyoake
mesh_terms: D001752:Blast Crisis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D000066673:Cell Self Renewal / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction
chemical_list: D047428:Protein Kinase Inhibitors
keywords: CML; Self-renewal; leukaemic stem cells.; signalling