Abstract
The constitutive tyrosine kinase (TK) activity of the Bcr-Abl fusion oncoprotein, the product of the Philadelphia (Ph1)-chromosome, is essential for factor-independent cell proliferation and survival in Bcr-Abl-positive (Bcr-Abl+) leukemias, such as chronic myelogenous leukemia (CML) or Ph1-positve acute leukemias. Currently, Bcr-Abl TK inhibitors (TKIs) such as imatinib mesylate are regarded as the most promising therapeutic strategy for Bcr-Abl+ leukemias, but recent evidence suggests that Bcr-Abl TKIs are unlikely to lead ultimately to complete elimination of leukemic cells. To develop more effective therapeutic strategies for complete leukemia cell elimination, it is essential to understand how cellular life and death decisions are regulated in Bcr-Abl+ leukemias. This paper reviews recent knowledge related to the biologic and molecular regulatory mechanisms for cellular survival and death under Bcr-Abl signaling control in leukemic cells, and focuses on Bcl-2 family-regulated apoptosis, especially on the role of BH3-only proteins, such as Bim, as well as on non-apoptotic programmed cell death, and autophagy. Implications for future therapeutic strategies for Bcr-Abl+ leukemia are also discussed.
Keywords: Apoptosis, autophagy, Bcl-2 family, Bcr-Abl, leukemia
Current Cancer Therapy Reviews
Title: Life and Death of Leukemic Cells Under Bcr-Abl Signaling Control
Volume: 5 Issue: 4
Author(s): Junya Kuroda and Masafumi Taniwaki
Affiliation:
Keywords: Apoptosis, autophagy, Bcl-2 family, Bcr-Abl, leukemia
Abstract: The constitutive tyrosine kinase (TK) activity of the Bcr-Abl fusion oncoprotein, the product of the Philadelphia (Ph1)-chromosome, is essential for factor-independent cell proliferation and survival in Bcr-Abl-positive (Bcr-Abl+) leukemias, such as chronic myelogenous leukemia (CML) or Ph1-positve acute leukemias. Currently, Bcr-Abl TK inhibitors (TKIs) such as imatinib mesylate are regarded as the most promising therapeutic strategy for Bcr-Abl+ leukemias, but recent evidence suggests that Bcr-Abl TKIs are unlikely to lead ultimately to complete elimination of leukemic cells. To develop more effective therapeutic strategies for complete leukemia cell elimination, it is essential to understand how cellular life and death decisions are regulated in Bcr-Abl+ leukemias. This paper reviews recent knowledge related to the biologic and molecular regulatory mechanisms for cellular survival and death under Bcr-Abl signaling control in leukemic cells, and focuses on Bcl-2 family-regulated apoptosis, especially on the role of BH3-only proteins, such as Bim, as well as on non-apoptotic programmed cell death, and autophagy. Implications for future therapeutic strategies for Bcr-Abl+ leukemia are also discussed.
Export Options
About this article
Cite this article as:
Kuroda Junya and Taniwaki Masafumi, Life and Death of Leukemic Cells Under Bcr-Abl Signaling Control, Current Cancer Therapy Reviews 2009; 5 (4) . https://dx.doi.org/10.2174/157339409789712726
DOI https://dx.doi.org/10.2174/157339409789712726 |
Print ISSN 1573-3947 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6301 |
Call for Papers in Thematic Issues
Current progress in Protein Degradation and Cancer Therapy
argeted Protein Degradation is gaining momentum in cancer therapy, it facilitate targeting undruggable proteins, it overcome cancer resistance and avoid undesirable side effects. Thus small molecules degraders have emerged as novel therapeutic strategy. Targeted protein degradation (TPD), the process of eliminating a protein of interest hold a great promise for ...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
-
Factors Controlling Chromatin Organization and Nucleosome Positioning for Establishment and Maintenance of HIV Latency
Current HIV Research Immunotherapy with Tumor Vaccines for the Treatment of Malignant Gliomas
Current Drug Discovery Technologies HDAC Inhibitors as Novel Anti-Cancer Therapeutics
Recent Patents on Anti-Cancer Drug Discovery Pgp and FLT3: Identification and Modulation of Two Proteins that Lead to Chemotherapy Resistance in Acute Myeloid Leukemia
Current Medicinal Chemistry Functional Nanoplatforms for Enhancement of Chemotherapeutic Index
Anti-Cancer Agents in Medicinal Chemistry Therapeutic Potential of Endophytic Compounds: A Special Reference to Drug Transporter Inhibitors
Current Topics in Medicinal Chemistry Tyrosine Kinase Inhibitors for the Treatment of Chronic Myeloid Leukemia
Anti-Cancer Agents in Medicinal Chemistry Immunomodulatory Drugs (IMiDs) in Multiple Myeloma
Current Cancer Drug Targets Dual-target Inhibitors Based on BRD4: Novel Therapeutic Approaches for Cancer
Current Medicinal Chemistry Busulfan Use in Hematopoietic Stem Cell Transplantation: Pharmacology, Dose Adjustment, Safety and Efficacy in Adults and Children
Current Drug Safety MicroRNAs as Main Players in the Pathogenesis of Chronic Lymphocytic Leukemia
MicroRNA Chemical and physical factors influencing the dynamics of differentiation in embryonic stem cells
Current Stem Cell Research & Therapy 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 Eosinophils in Cancer: Favourable or Unfavourable?
Current Medicinal Chemistry The Role of Peptidyl Prolyl Isomerases in Aging and Vascular Diseases
Current Molecular Pharmacology Acute Myeloid Leukemia in the Elderly: Current Therapeutic Results and Perspectives for Clinical Research
Reviews on Recent Clinical Trials Notch-Associated MicroRNAs in Cancer
Current Drug Targets The Development of Cytokine Receptor Antagonists as Potential Therapeutic Agents for the Myeloproliferative Disorders
Current Pharmaceutical Design On the Origin of Epidermal Cancers
Current Molecular Medicine Kavalactone Pharmacophores for Major Cellular Drug Targets
Mini-Reviews in Medicinal Chemistry