Abstract
Various signal transduction pathways have been implicated in the pathogenesis of chronic lymphocytic leukemia (CLL), which is characterized by the progressive accumulation of monoclonal CD5+ B cells in the blood. B cell receptor (BCR) signaling appears to have a crucial role in disease onset and is thought to be induced by self or non-self-antigen recognition leading to chronic stimulation. Several of the kinases functioning downstream of the BCR are aberrantly expressed or constitutively activated in CLL. Yet, these kinases have additional roles, particularly in chemokine receptor signaling, which is essential for homing and survival of CLL cells in lymphoid organs, or in toll-like receptor signaling. Recently, small molecule inhibitors of kinases in the BCR signaling pathway have shown impressive anti-tumor activity in clinical trials. Remarkably, the observed durable responses in CLL patients were accompanied by transient increases in blood lymphocyte numbers, indicating the importance of these kinases in chemokine receptor signaling. In this review, we therefore highlight the role of BCR signaling and the important other associated signal transduction cascades for CLL cells and give an overview of novel agents that target these specific pathways and were shown to be successful for CLL treatment in clinical trials.
Keywords: B cell receptor, BTK, Chronic lymphocytic leukemia, kinase inhibitors, signal transduction.
Current Cancer Drug Targets
Title:Targeting Signaling Pathways in Chronic Lymphocytic Leukemia
Volume: 16 Issue: 8
Author(s): Alice F. Muggen, Simar P. Singh, Rudi W. Hendriks and Anton W. Langerak
Affiliation:
Keywords: B cell receptor, BTK, Chronic lymphocytic leukemia, kinase inhibitors, signal transduction.
Abstract: Various signal transduction pathways have been implicated in the pathogenesis of chronic lymphocytic leukemia (CLL), which is characterized by the progressive accumulation of monoclonal CD5+ B cells in the blood. B cell receptor (BCR) signaling appears to have a crucial role in disease onset and is thought to be induced by self or non-self-antigen recognition leading to chronic stimulation. Several of the kinases functioning downstream of the BCR are aberrantly expressed or constitutively activated in CLL. Yet, these kinases have additional roles, particularly in chemokine receptor signaling, which is essential for homing and survival of CLL cells in lymphoid organs, or in toll-like receptor signaling. Recently, small molecule inhibitors of kinases in the BCR signaling pathway have shown impressive anti-tumor activity in clinical trials. Remarkably, the observed durable responses in CLL patients were accompanied by transient increases in blood lymphocyte numbers, indicating the importance of these kinases in chemokine receptor signaling. In this review, we therefore highlight the role of BCR signaling and the important other associated signal transduction cascades for CLL cells and give an overview of novel agents that target these specific pathways and were shown to be successful for CLL treatment in clinical trials.
Export Options
About this article
Cite this article as:
Muggen F. Alice, Singh P. Simar, Hendriks W. Rudi and Langerak W. Anton, Targeting Signaling Pathways in Chronic Lymphocytic Leukemia, Current Cancer Drug Targets 2016; 16 (8) . https://dx.doi.org/10.2174/1568009616666160408145623
DOI https://dx.doi.org/10.2174/1568009616666160408145623 |
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
-
Development of Anti-CD20 Antigen-Targeting Therapies for B-cell Lymphoproliferative Malignancies - The State of the Art
Current Drug Targets Performance of Feature Selection Methods
Current Genomics Effect of Treatment with Caspofungin on the Diagnosis of Fungal Infections by Gamma Scintigraphy
Current Radiopharmaceuticals Making Sense of Molecular Signatures in The Immune System
Combinatorial Chemistry & High Throughput Screening Is DNA Minor Groove Binding Crucial for Biological Activity of Triazoloacridinones with Cytotoxic and Antitumour Properties?
Letters in Drug Design & Discovery T-Cell Zeta Chain Expression, Phosphorylation and Degradation and their Role in T-Cell Signal Transduction and Immune Response Regulation in Health And Disease
Current Signal Transduction Therapy Histone Deacetylase Inhibitors: Potent Anti-Leukemic Agents
Current Medicinal Chemistry A Virtual Screening Approach for the Identification of High Affinity Small Molecules Targeting BCR-ABL1 Inhibitors for the Treatment of Chronic Myeloid Leukemia
Current Topics in Medicinal Chemistry The Function and Regulation of BMP6 in Various Kinds of Stem Cells
Current Pharmaceutical Design Novel Therapeutic Agents Against Cancer Stem Cells of Chronic Myeloid Leukemia
Anti-Cancer Agents in Medicinal Chemistry Advances in the Management of Brain Tumors in Infants
Current Cancer Therapy Reviews Cancer Stem Cells: How can we Target them?
Current Medicinal Chemistry Liposomal-All-trans-Retinoic Acid in the Treatment of Acute Promyelocytic Leukemia
Current Cancer Therapy Reviews Use of Single Nucleotide Polymorphism Array Technology to Improve the Identification of Chromosomal Lesions in Leukemia
Current Cancer Drug Targets The Genetic Landscapes of Inflammation-Driven Gastrointestinal Tract Cancers
Current Pharmaceutical Design The Molecular Bases of the Self-Renewal and Differentiation of Leukemic Stem Cells
Current Cancer Therapy Reviews Synthesis and Antiproliferative Evaluation of Spirothiadiazolopyridazine Derivatives
Letters in Drug Design & Discovery B7-H3-targeted Radioimmunotherapy of Human Cancer
Current Medicinal Chemistry Recent Developments Towards the Synthesis of Varitriol: An Antitumour Agent from Marine Derived Fungus Emericella Variecolor
Current Organic Synthesis MicroRNAs in Tumorigenesis
Current Pharmaceutical Biotechnology