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.
Graphical Abstract
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 |
Related Books
![](/images/wayfinder.jpg)
- Author Guidelines
- Bentham Author Support Services (BASS)
- 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
-
A Scientometrics Analysis and Visualization of Depressive Disorder
Current Neuropharmacology Ofatumumab: A Novel Anti-CD20 Monoclonal Antibody for the Treatment of Chronic Lymphocytic Leukemia
Current Drug Therapy Histone Deacetylase Inhibitors: Potent Anti-Leukemic Agents
Current Medicinal Chemistry ROS1 Kinase Inhibitors for Molecular-Targeted Therapies
Current Medicinal Chemistry Cancer “Stemness”- Regulating MicroRNAs: Role, Mechanisms and Therapeutic Potential
Current Drug Targets Adverse Reactions Induced by Minocycline: A Review of Literature
Current Drug Safety Double-Strand Breaks Repair by Non-Homologous DNA End Joining in Mammalian Cells
Current Genomics Structural and Functional Role of Gly281 in L-asparaginase from Erwinia carotovora
Protein & Peptide Letters Editorial (Thematic Issue: Chronic Myeloid Leukemia: Reaching For the Cure)
Current Cancer Drug Targets Nitrogen-Containing Heterocycles as Anticancer Agents: An Overview
Anti-Cancer Agents in Medicinal Chemistry Protective Effect of Heat Shock Proteins in the Nervous System
Current Neurovascular Research Organic Synthesis and Antisense Effects of Oligonucleotide-Peptide Conjugates
Current Organic Chemistry Epigenetics in Medullary Thyroid Cancer: From Pathogenesis to Targeted Therapy
Recent Patents on Anti-Cancer Drug Discovery Bladder Cancer: Update on Risk Factors, Molecular and Ultrastructural Patterns
Current Medicinal Chemistry Chalcone Derivatives Activate and Desensitize the Transient Receptor Potential Ankyrin 1 Cation Channel, Subfamily A, Member 1 TRPA1 Ion Channel: Structure-Activity Relationships in vitro and Anti-Nociceptive and Anti-inflammatory Activity in vivo
CNS & Neurological Disorders - Drug Targets Optimization on Fc for Improvement of Stability and Aggregation Resistance
Current Pharmaceutical Biotechnology Role of MicroRNA in the Diagnosis and Therapy of Hepatocellular Carcinoma: A New Frontier
MicroRNA Targeting Apoptosis Pathway with Natural Terpenoids: Implications for Treatment of Breast and Prostate Cancer
Current Drug Targets The Phosphoinositide 3-Kinase Pathway in Human Cancer: Genetic Alterations and Therapeutic Implications
Current Genomics Carcinogenesis and Therapeutic Strategies in Thyroid Cancer
Current Drug Targets