Title:Stem Cell Guardians – Old and New Perspectives in LSC Biology
Volume: 18
Issue: 4
Author(s): Gillian A. Horne, Lorna Jackson, Vignir Helgason and Tessa L. Holyoake
Affiliation:
Keywords:
Self-renewal, signalling, CML, leukaemic stem cells.
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.
