Abstract
Chronic myeloid leukemia (CML) is a myeloproliferative disorder caused by the Philadelphia-positive chromosome deriving from a translocation between chromosomes 22 and 9. The oncogenic product of this aberrant chromosome is the constitutively active tyrosine kinase BCR-ABL that is responsible for leukemic cell growth, proliferation and survival driven by the dysregulation of a large array of signal transduction pathways. Inhibition of BCRABL with tyrosine kinase inhibitors proved to be an efficient therapy of CML in the chronic phase. Unfortunately, the impressive success of BCR-ABL inhibitors as front-line therapy in CML has been tempered by problems of disease persistence or relapse arising from different mechanisms, including mutations in the kinase domain of the enzyme BCRABL and mechanisms independent from BCR-ABL activity. Growing evidence has also suggested a pivotal role of persistent leukemic cancer stem cells, characterized by high self-renewal and pluripotency, in CML maintenance and/or relapse. The present review deals with the most recent advances in this challenging field and focuses on the development of new drugs and therapeutic approaches to eradicate the subtle and dangerous leukemic stem cells responsible for maintaining and sustaining tumor growth.
Keywords: BCR-ABL, chronic myeloid leukemia, leukemic stem cells, tyrosine kinase inhibitors
Current Cancer Drug Targets
Title:New Strategies in the Chemotherapy of Leukemia: Eradicating Cancer Stem Cells in Chronic Myeloid Leukemia
Volume: 12 Issue: 5
Author(s): A. Stefanachi, F. Leonetti, O. Nicolotti, M. Catto, L. Pisani, S. Cellamare, C. Altomare and A. Carotti
Affiliation:
Keywords: BCR-ABL, chronic myeloid leukemia, leukemic stem cells, tyrosine kinase inhibitors
Abstract: Chronic myeloid leukemia (CML) is a myeloproliferative disorder caused by the Philadelphia-positive chromosome deriving from a translocation between chromosomes 22 and 9. The oncogenic product of this aberrant chromosome is the constitutively active tyrosine kinase BCR-ABL that is responsible for leukemic cell growth, proliferation and survival driven by the dysregulation of a large array of signal transduction pathways. Inhibition of BCRABL with tyrosine kinase inhibitors proved to be an efficient therapy of CML in the chronic phase. Unfortunately, the impressive success of BCR-ABL inhibitors as front-line therapy in CML has been tempered by problems of disease persistence or relapse arising from different mechanisms, including mutations in the kinase domain of the enzyme BCRABL and mechanisms independent from BCR-ABL activity. Growing evidence has also suggested a pivotal role of persistent leukemic cancer stem cells, characterized by high self-renewal and pluripotency, in CML maintenance and/or relapse. The present review deals with the most recent advances in this challenging field and focuses on the development of new drugs and therapeutic approaches to eradicate the subtle and dangerous leukemic stem cells responsible for maintaining and sustaining tumor growth.
Export Options
About this article
Cite this article as:
Stefanachi A., Leonetti F., Nicolotti O., Catto M., Pisani L., Cellamare S., Altomare C. and Carotti A., New Strategies in the Chemotherapy of Leukemia: Eradicating Cancer Stem Cells in Chronic Myeloid Leukemia, Current Cancer Drug Targets 2012; 12 (5) . https://dx.doi.org/10.2174/156800912800673239
DOI https://dx.doi.org/10.2174/156800912800673239 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
- 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
-
Contrast Enhanced Sonography for Diagnosis of (Peri-) Splenic Pathology
Current Medical Imaging The Metabolomic Strategy in Tuberculosis Therapy
Combinatorial Chemistry & High Throughput Screening Current Perspectives on Anti-Aging Interventions
Letters in Drug Design & Discovery Therapeutic Antibodies
Current Molecular Medicine Cytoplasmic CXCR4 High-Expression Exhibits Distinct Poor Clinicopathological Characteristics and Predicts Poor Prognosis in Triple-Negative Breast Cancer
Current Molecular Medicine β-lactam Structured, 4-(4-(Methylsulfonyl)phenyl)-1-pentyl-3-phenoxyazetidin-2-one: Selectively Targets Cancerous B Lymphocyte Mitochondria
Anti-Cancer Agents in Medicinal Chemistry Dissecting Bortezomib: Development, Application, Adverse Effects and Future Direction
Current Pharmaceutical Design Polymer-Drug Nanoconjugate – An Innovative Nanomedicine: Challenges and Recent Advancements in Rational Formulation Design for Effective Delivery of Poorly Soluble Drugs
Pharmaceutical Nanotechnology Characterizing the Relationship Between the Chemical Structures of Drugs and their Activities on Primary Cultures of Pediatric Solid Tumors
Current Medicinal Chemistry Glyoxalase 1 and 2 Enzyme Inhibitory Activity of 6-Sulfamoylsaccharin and Sulfocoumarin Derivates
Letters in Drug Design & Discovery T Cell Redirecting Therapies for Cancer Treatment
Current Cancer Drug Targets In Vitro Antitumoral Activity of Palladium(II) and Platinum(II) Complexes with O,O'-Dialkyl Esters of Ethylene-bis(S)-Leucine
Letters in Drug Design & Discovery Economics of Pharmacogenomics: Rethinking Beyond QALYs?
Current Pharmacogenomics and Personalized Medicine Non-Genotoxic p53-Activators and their Significance as Antitumor Therapy of Future
Current Medicinal Chemistry Cancer Prevention with Promising Natural Products: Mechanisms of Action and Molecular Targets
Anti-Cancer Agents in Medicinal Chemistry Experimental Strategies in Autoimmunity: Antagonists of Cytokines and their Receptors, Nanocarriers, Inhibitors of Immunoproteasome, Leukocyte Migration and Protein Kinases
Current Pharmaceutical Design Patent Selections
Recent Patents on Anti-Cancer Drug Discovery Distinct Epigenetic Reprogramming, Mitochondrial Patterns, Cellular Morphology, and Cytotoxicity after Bee Venom Treatment
Recent Patents on Anti-Cancer Drug Discovery Current Developments of Coumarin Compounds in Medicinal Chemistry
Current Pharmaceutical Design Ras Dimer Formation as a New Signaling Mechanism and Potential Cancer Therapeutic Target
Mini-Reviews in Medicinal Chemistry