Stem cell guardians – old and new perspectives in LSC biology

Horne, G. , Jackson, L. , Helgason, V. and Holyoake, T. L. (2017) Stem cell guardians – old and new perspectives in LSC biology. Current Drug Targets, 18(4), pp. 405-413. (doi: 10.2174/1389450117666160712092944) (PMID:27411711)

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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.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Horne, Dr Gillian and Holyoake, Professor Tessa and Jackson, Lorna and Helgason, Professor Vignir
Authors: Horne, G., Jackson, L., Helgason, V., and Holyoake, T. L.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Current Drug Targets
Publisher:Bentham Science Publishers
Published Online:11 July 2016

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