Abstract
Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease characterized by the accumulation/expansion of a clonal population of neoplastic cells with the morphological appearance of small mature B lymphocytes in blood, bone marrow, and lymphoid organs. CD49d, the α chain of the α4β1 integrin heterodimer, is one of the main interactors between CLL cells and accessory cells in the microenvironmental sites and one of the main predictors of overall survival. In particular, CD49d is known to play a pivotal role in mediating both cell-cell and cell-matrix interactions in CLL-involved tissues eventually delivering prosurvival signals and protecting CLL cells from drug-induced damages. Treatment strategies targeting the α4β1 integrin could represent an interesting option in CLL. In this context, the recombinant anti-CD49d antibody natalizumab demonstrated the potential to overcome stromal cell-induced resistance of B cell lymphoma cells against cytotoxic drugs and rituximab in vitro. Moreover, a specific interest for the CD49d molecule raises from the clinical activity of the recently proposed inhibitors of kinases downstream the BCR that has been recently related with the inside-out activation of the α4β1 integrin. In the review, we addressed in detail the role of CD49d in CLL cells, including clinical impact, relationship with specific cytogenetic features, and CD49d-dependent interactions in lymph node and bone marrow microenvironment responsible for growth- and survival- supporting signals, eventually influencing CLL prognosis and therapeutic options.
Keywords: CD49d, CLL, integrin, microenvironment, prognosis, therapy.
Current Cancer Drug Targets
Title:Functional and Clinical Significance of the Integrin Alpha Chain CD49d Expression in Chronic Lymphocytic Leukemia
Volume: 16 Issue: 8
Author(s): Michele Dal Bo, Erika Tissino, Dania Benedetti, Chiara Caldana, Riccardo Bomben, Giovanni Del Poeta, Gianluca Gaidano, Francesca Maria Rossi, Pietro Bulian, Antonella Zucchetto and Valter Gattei
Affiliation:
Keywords: CD49d, CLL, integrin, microenvironment, prognosis, therapy.
Abstract: Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease characterized by the accumulation/expansion of a clonal population of neoplastic cells with the morphological appearance of small mature B lymphocytes in blood, bone marrow, and lymphoid organs. CD49d, the α chain of the α4β1 integrin heterodimer, is one of the main interactors between CLL cells and accessory cells in the microenvironmental sites and one of the main predictors of overall survival. In particular, CD49d is known to play a pivotal role in mediating both cell-cell and cell-matrix interactions in CLL-involved tissues eventually delivering prosurvival signals and protecting CLL cells from drug-induced damages. Treatment strategies targeting the α4β1 integrin could represent an interesting option in CLL. In this context, the recombinant anti-CD49d antibody natalizumab demonstrated the potential to overcome stromal cell-induced resistance of B cell lymphoma cells against cytotoxic drugs and rituximab in vitro. Moreover, a specific interest for the CD49d molecule raises from the clinical activity of the recently proposed inhibitors of kinases downstream the BCR that has been recently related with the inside-out activation of the α4β1 integrin. In the review, we addressed in detail the role of CD49d in CLL cells, including clinical impact, relationship with specific cytogenetic features, and CD49d-dependent interactions in lymph node and bone marrow microenvironment responsible for growth- and survival- supporting signals, eventually influencing CLL prognosis and therapeutic options.
Export Options
About this article
Cite this article as:
Bo Dal Michele, Tissino Erika, Benedetti Dania, Caldana Chiara, Bomben Riccardo, Poeta Del Giovanni, Gaidano Gianluca, Rossi Maria Francesca, Bulian Pietro, Zucchetto Antonella and Gattei Valter, Functional and Clinical Significance of the Integrin Alpha Chain CD49d Expression in Chronic Lymphocytic Leukemia, Current Cancer Drug Targets 2016; 16 (8) . https://dx.doi.org/10.2174/1568009616666160809102219
DOI https://dx.doi.org/10.2174/1568009616666160809102219 |
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
-
The Role of Cancer Biomarkers in HIV Infected Hosts
Current Medicinal Chemistry Carbohydrates: Potential Sweet Tools Against Cancer
Current Medicinal Chemistry Identification of Molecular Targets Associated with Ethanol Toxicity and Implications in Drug Development
Current Pharmaceutical Design Photodynamic Therapy: The Development of New Photosensitisers
Anti-Cancer Agents in Medicinal Chemistry Irreversible Kinase Inhibitors Targeting Cysteine Residues and their Applications in Cancer Therapy
Mini-Reviews in Medicinal Chemistry Aluminofluoride Complexes: Phosphate Analogues and a Hidden Hazard for Living Organisms
Current Inorganic Chemistry (Discontinued) Clinical Approaches to Immunotherapy in Non-Small Cell Lung Cancer: Current and Future Perspectives
Current Molecular Pharmacology Chemotherapeutic Targeting of Cell Death Pathways
Anti-Cancer Agents in Medicinal Chemistry B Lymphocyte Memory in X-Linked Lymphoproliferative Disease (XLP)
Current Immunology Reviews (Discontinued) Current Treatment Concepts of CML
Current Cancer Drug Targets Review of Clinic Trials: Agents Targeting c-Met
Reviews on Recent Clinical Trials Anticancer Activity and DNA Binding of 4-Alkylenediamines Modified Naphthalimide Derivatives
Letters in Drug Design & Discovery NAD+ Metabolism and NAD+-Dependent Enzymes: Promising Therapeutic Targets for Neurological Diseases
Current Drug Targets Tissue Elasticity Bridges Cancer Stem Cells to the Tumor Microenvironment Through microRNAs: Implications for a “Watch-and-Wait” Approach to Cancer
Current Stem Cell Research & Therapy From Stem Cell Biology to The Treatment of Lung Diseases
Current Stem Cell Research & Therapy Quantifying Gp96/Grp94 Complexes Preparations for Vaccines: a Key Step Often Inaccurate
Current Medicinal Chemistry The Role of CD40 Expression in Dendritic Cells in Cancer Biology; A Systematic Review
Current Cancer Drug Targets Insight to Physiology and Pathology of Zinc(II) Ions and Their Actions in Breast and Prostate Carcinoma
Current Medicinal Chemistry Proteasome Inhibitors Therapeutic Strategies for Cancer
Recent Patents on Anti-Cancer Drug Discovery Reversal of Tumor Induced Dendritic Cell Paralysis: A Treatment Regimen Against Cancer
Current Immunology Reviews (Discontinued)