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 |
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
-
Bruton's Tyrosine Kinase Inhibition in the Treatment of Preclinical Models
and Multiple Sclerosis
Current Pharmaceutical Design Retinoids as Critical Modulators of Immune Functions: New Therapeutic Perspectives for Old Compounds
Endocrine, Metabolic & Immune Disorders - Drug Targets Chemical Space of FLT3 Inhibitors as Potential Anti-AML Drugs
Recent Patents on Anti-Cancer Drug Discovery The Use of Cytokines and Chemokines in the Cancer Immunotherapy
Recent Patents on Anti-Cancer Drug Discovery Composite Lymphomas: A Challenging Entity
Current Cancer Therapy Reviews SENP1 as A Biomarker for the Diagnosis of Cancer: Review of the Science and Published Patents
Recent Patents on Biomarkers Status of Non-Classical Mononuclear Platinum Anticancer Drug Development
Mini-Reviews in Medicinal Chemistry Glioma Stem Cell Maintenance: The Role of the Microenvironment
Current Pharmaceutical Design Thiopurine S-Methyltransferase as a Pharmacogenetic Biomarker: Significance of Testing and Review of Major Methods
Cardiovascular & Hematological Agents in Medicinal Chemistry The Frequency of Thrombotic Events Among Adults Given Antifibrinolytic Drugs for Spontaneous Bleeding: Systematic Review and Meta-Analysis of Observational Studies and Randomized Trials
Current Drug Safety Pharmacokinetics-Pharmacology Disconnection of Herbal Medicines and its Potential Solutions with Cellular Pharmacokinetic-Pharmacodynamic Strategy
Current Drug Metabolism Advances in Cancer Stem Cell Therapy: Targets and Treatments
Recent Patents on Regenerative Medicine Insulin-Like Growth Factor 1 Receptor Targeted Therapeutics: Novel Compounds and Novel Treatment Strategies for Cancer Medicine
Recent Patents on Anti-Cancer Drug Discovery The Ovary Feels Fine when Paracrine and Autocrine Networks Cooperate with Gonadotropins in the Regulation of Folliculogenesis
Current Pharmaceutical Design Recent Patents on the Identification and Clinical Application of microRNAs and Target Genes
Recent Patents on DNA & Gene Sequences Retrospective Observational Study to Evaluate Causality, Preventability and Severity of Adverse Drug Reaction Associated with Anticancer Drugs in a Tertiary Care Hospital in Northern India
Current Drug Safety Targeted Therapy for Advanced Renal Cell Cancer: Cytokines and Beyond
Current Pharmaceutical Design Novel Rational Drug Design Strategies with Potential to Revolutionize Malaria Chemotherapy
Current Medicinal Chemistry Impact of Splicing Factor Mutations on Pre-mRNA Splicing in the Myelodysplastic Syndromes
Current Pharmaceutical Design The Efficacy of Vitamin K, A Member Of Naphthoquinones in the Treatment of Cancer: A Systematic Review and Meta-Analysis
Current Cancer Drug Targets