Abstract
Although the imatinib based therapy of chronic myeloid leukemia (CML) represents a triumph of medicine, not all patients with CML benefit from this drug due to the development of resistance and intolerance. The interruption of imatinib treatment is often followed by clinical relapse, suggesting a failure in the killing of residual leukaemic stem cells. There is need to identify alternative selective molecular targets for this disease and develop more effective therapeutic approaches. Alternative pre-mRNA splicing (AS) is an epigenetic process that greatly diversifies the repertoire of the transcriptome. AS orchestrates interactions between various types of proteins and between proteins and nucleic acids. Changes caused by individual splicing events in the cells are small, however, “splicing programs” typically react to these individual changes with considerable effects in cell proliferation, cell survival, and apoptosis. Current evidence suggests a pivotal role of AS in leukemias, particularly in myelodisplastic syndrome (MDS) and chronic lymphocyte leukemia (CLL). From these studies and studies in other malignances, it is clear that splicing abnormalities play a significant role in malignant transformation. Evaluation of AS events in CML can be used to identify novel disease markers and drugsensitive targets to overcome the limits of the small molecule inhibitors currently used for treating patients with CML. The use of aberrant splice variants as disease markers has been reported, however, little is known about the use of splicing abnormalities as drug targets in CML. Herein we discuss potential therapeutic approaches that can be used to target splicing abnormalities in CML.
Keywords: Alternative splicing, BCR-ABL, bio-markers, chronic myeloid leukemia, therapeutic targets.
Current Cancer Drug Targets
Title:Alternative Splicing in Chronic Myeloid Leukemia (CML): A Novel Therapeutic Target?
Volume: 13 Issue: 7
Author(s): Sophia Adamia, Patrick M. Pilarski, Michal Bar-Natan, Richard M. Stone and James D. Griffin
Affiliation:
Keywords: Alternative splicing, BCR-ABL, bio-markers, chronic myeloid leukemia, therapeutic targets.
Abstract: Although the imatinib based therapy of chronic myeloid leukemia (CML) represents a triumph of medicine, not all patients with CML benefit from this drug due to the development of resistance and intolerance. The interruption of imatinib treatment is often followed by clinical relapse, suggesting a failure in the killing of residual leukaemic stem cells. There is need to identify alternative selective molecular targets for this disease and develop more effective therapeutic approaches. Alternative pre-mRNA splicing (AS) is an epigenetic process that greatly diversifies the repertoire of the transcriptome. AS orchestrates interactions between various types of proteins and between proteins and nucleic acids. Changes caused by individual splicing events in the cells are small, however, “splicing programs” typically react to these individual changes with considerable effects in cell proliferation, cell survival, and apoptosis. Current evidence suggests a pivotal role of AS in leukemias, particularly in myelodisplastic syndrome (MDS) and chronic lymphocyte leukemia (CLL). From these studies and studies in other malignances, it is clear that splicing abnormalities play a significant role in malignant transformation. Evaluation of AS events in CML can be used to identify novel disease markers and drugsensitive targets to overcome the limits of the small molecule inhibitors currently used for treating patients with CML. The use of aberrant splice variants as disease markers has been reported, however, little is known about the use of splicing abnormalities as drug targets in CML. Herein we discuss potential therapeutic approaches that can be used to target splicing abnormalities in CML.
Export Options
About this article
Cite this article as:
Adamia Sophia, Pilarski M. Patrick, Bar-Natan Michal, Stone M. Richard and Griffin D. James, Alternative Splicing in Chronic Myeloid Leukemia (CML): A Novel Therapeutic Target?, Current Cancer Drug Targets 2013; 13 (7) . https://dx.doi.org/10.2174/15680096113139990083
DOI https://dx.doi.org/10.2174/15680096113139990083 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...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
-
Restoring TRAIL Induced Apoptosis Using Naturopathy. Hercules Joins Hand with Nature to Triumph Over Lernaean Hydra
Current Genomics In Search of Natural Remediation for Cervical Cancer
Anti-Cancer Agents in Medicinal Chemistry A panoramic view of chronic liver diseases and natural remedies reported in Traditional Persian Medicine
Current Pharmaceutical Design Non-Genotoxic p53-Activators and their Significance as Antitumor Therapy of Future
Current Medicinal Chemistry Evaluation of the in vitro Chemosensitivity and Correlation with Clinical Outcomes in Lung Cancer using the ATP-TCA
Anti-Cancer Agents in Medicinal Chemistry The Use of Cytokines and Chemokines in the Cancer Immunotherapy
Recent Patents on Anti-Cancer Drug Discovery Lipid-based Nano-phytomedicines for Disease Treatment and Theranostic Applications
Current Nanomedicine May Patients with Alcohol Liver Disease Benefit from Herbal Medicines?
Reviews on Recent Clinical Trials Synthesis of Pyrophosphate-Containing Compounds that Stimulate VγVδ2 T Cells: Application to Cancer Immunotherapy
Medicinal Chemistry Radiation-Induced Bystander and other Non-Targeted Effects: Novel Intervention Points in Cancer Therapy?
Current Cancer Drug Targets Regulation of EMT by Notch Signaling Pathway in Tumor Progression
Current Cancer Drug Targets Meet Our Editorial Board Member:
Current Medicinal Chemistry Role of Unani Medicines in Cancer Control and Management
Current Drug Therapy Natural Compounds in Anti-Leukaemic Therapy: A Review
Mini-Reviews in Medicinal Chemistry Multifunctional Proteins in Tumorigenesis: Aminoacyl-tRNA Synthetases and Translational Components
Current Proteomics Nanosponges Encapsulated Phytochemicals for Targeting Cancer: A Review
Current Drug Targets Anti-cancer Peptides from Ras-P21 and P53 Proteins
Current Pharmaceutical Design Functions of Antimicrobial Peptides in Vertebrates
Current Protein & Peptide Science Characterization of Particulate Drug Delivery Systems for Oral Delivery of Peptide and Protein Drugs
Current Pharmaceutical Design When BMP Signalling Goes Wrong: The Intracellular and Molecular Mechanisms of BMP Signalling in Cancer
Current Signal Transduction Therapy