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.
Keywords: Self-renewal, signalling, CML, leukaemic stem cells.
Current Drug Targets
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.
Export Options
About this article
Cite this article as:
Horne A. Gillian, Jackson Lorna, Helgason Vignir and Holyoake L. Tessa, Stem Cell Guardians – Old and New Perspectives in LSC Biology, Current Drug Targets 2017; 18 (4) . https://dx.doi.org/10.2174/1389450117666160712092944
DOI https://dx.doi.org/10.2174/1389450117666160712092944 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
Call for Papers in Thematic Issues
New drug therapy for eye diseases
Eyesight is one of the most critical senses, accounting for over 80% of our perceptions. Our quality of life might be significantly affected by eye disease, including glaucoma, diabetic retinopathy, dry eye, etc. Although the development of microinvasive ocular surgery reduces surgical complications and improves overall outcomes, medication therapy is ...read more
RNA Molecules in the Treatment of Human Diseases
Messenger and non-coding RNAs, including long and small transcripts, are mediators of gene expression. Gene expression at the RNA level shows significant aberrations in human diseases, including cancer, leukemia, lymphoma, cardiovascular diseases, and neurological disorders. Human transcripts serve either as biomarkers of diagnosis, prognosis, prediction of treatment response and/or therapy ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Bruton Kinase Inhibitors in Chronic Lymphocytic Leukemia
Anti-Cancer Agents in Medicinal Chemistry Genetic Manipulation of Human Embryonic Stem Cells: A System to Study Early Human Development and Potential Therapeutic Applications
Current Gene Therapy Nitrogen-Containing Heterocycles as Anticancer Agents: An Overview
Anti-Cancer Agents in Medicinal Chemistry Impact of Immunogenetic Polymorphisms in Bone Marrow Failure Syndromes
Mini-Reviews in Medicinal Chemistry CXCL12-CXCR4 Axis in Angiogenesis, Metastasis and Stem Cell Mobilization
Current Pharmaceutical Design Design of New Drug Molecules to be Used in Reversing Multidrug Resistance in Cancer Cells
Current Cancer Drug Targets Pentapeptides as Minimal Functional Units in Cell Biology and Immunology
Current Protein & Peptide Science An Antileukemic Glutaminase Free L-Asparaginase from Bacillus brevis
Current Biotechnology Sulfur Containing Acridine Derivatives in Preclinical Studies with Cancer Cell Lines
Current Medicinal Chemistry Pro-inflammatory Cytokines in Animal and Human Gestation
Current Pharmaceutical Design Metabolism and Distribution of Novel Tumor Targeting Drugs In Vivo
Current Drug Metabolism The Role of AMPK/mTOR Modulators in the Therapy of Acute Myeloid Leukemia
Current Medicinal Chemistry Nonviral Vectors for Cancer Gene Therapy: Prospects for Integrating Vectors and Combination Therapies
Current Gene Therapy Steroidal Conjugates and Their Pharmacological Applications
Current Medicinal Chemistry Perspectives on Sesquiterpene Lactones in Inflammation and Cancer
Current Drug Targets Wnt/β-Catenin/LEF-1 Signaling in Chronic Lymphocytic Leukemia (CLL): A Target for Current and Potential Therapeutic Options
Current Cancer Drug Targets Inflammation and Anemia
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry α-Halogenoacrylic Derivatives of Antitumor Agents
Mini-Reviews in Medicinal Chemistry HOX Genes as Potential Markers of Circulating Tumour Cells
Current Molecular Medicine Microglia Phenotype Diversity
CNS & Neurological Disorders - Drug Targets