Abstract
By analyzing the cDNA obtained from 16 B-cell chronic lymphocytic leukemia (B-CLL) patient samples, we found that Nutlin-3, a small molecule inhibitor of MDM2/p53 interaction, induced a characteristic gene expression profile (GEP) signature in 13 out of 16 B-CLL samples. The lack of Nutlin-3-induced GEP signature in 3 out of 16 B-CLL samples was not due to p53 deletion and/or mutation, as demonstrated by FISH analysis and p53 sequencing. Of note, the 3 BCLL samples in which Nutlin-3 did not elicit the GEP signature were also less susceptible to Nutlin-3-mediated cytotoxicity with respect to the remaining 13 B-CLL samples. However, the partial lack of response in these p53 wild-type B-CLL samples was not due to defects in the ability of Nutlin-3 to promote p53 induction, as confirmed by the rapid accumulation of p53 protein at Western blot analysis in response to Nutlin-3 in all samples examined. Upon exposure to Nutlin-3, the genes up-regulated with the highest score in the majority of B-CLL cells were all known p53-target genes, including genes involved in apoptotic pathways, such as FAS and BAX, as well as MDM2. Taken together, our data indicate that the ability of Nutlin-3 to induce a characteristic GEP signature correlates with its cytotoxic potential in p53 wild-type BCLL cells. However, in some p53 wild-type B-CLL samples, the response to Nutlin-3 cannot be predicted on the basis of FISH analysis or p53 sequencing.
Keywords: B-CLL, Nutlin-3, p53 pathway, gene expression profile, MDM2
Current Cancer Drug Targets
Title: Exposure of B Cell Chronic Lymphocytic Leukemia (B-CLL) Cells to Nutlin-3 Induces a Characteristic Gene Expression Profile, which Correlates with Nutlin-3-Mediated Cytotoxicity (Supplementry Table)
Volume: 9 Issue: 4
Author(s): G. Zauli, M. G. di Iasio, P. Secchiero, M. Dal Bo, D. Marconi, R. Bomben, G. Del Poeta and V. Gattei
Affiliation:
Keywords: B-CLL, Nutlin-3, p53 pathway, gene expression profile, MDM2
Abstract: By analyzing the cDNA obtained from 16 B-cell chronic lymphocytic leukemia (B-CLL) patient samples, we found that Nutlin-3, a small molecule inhibitor of MDM2/p53 interaction, induced a characteristic gene expression profile (GEP) signature in 13 out of 16 B-CLL samples. The lack of Nutlin-3-induced GEP signature in 3 out of 16 B-CLL samples was not due to p53 deletion and/or mutation, as demonstrated by FISH analysis and p53 sequencing. Of note, the 3 BCLL samples in which Nutlin-3 did not elicit the GEP signature were also less susceptible to Nutlin-3-mediated cytotoxicity with respect to the remaining 13 B-CLL samples. However, the partial lack of response in these p53 wild-type B-CLL samples was not due to defects in the ability of Nutlin-3 to promote p53 induction, as confirmed by the rapid accumulation of p53 protein at Western blot analysis in response to Nutlin-3 in all samples examined. Upon exposure to Nutlin-3, the genes up-regulated with the highest score in the majority of B-CLL cells were all known p53-target genes, including genes involved in apoptotic pathways, such as FAS and BAX, as well as MDM2. Taken together, our data indicate that the ability of Nutlin-3 to induce a characteristic GEP signature correlates with its cytotoxic potential in p53 wild-type BCLL cells. However, in some p53 wild-type B-CLL samples, the response to Nutlin-3 cannot be predicted on the basis of FISH analysis or p53 sequencing.
Export Options
About this article
Cite this article as:
Zauli G., di Iasio G. M., Secchiero P., Dal Bo M., Marconi D., Bomben R., Del Poeta G. and Gattei V., Exposure of B Cell Chronic Lymphocytic Leukemia (B-CLL) Cells to Nutlin-3 Induces a Characteristic Gene Expression Profile, which Correlates with Nutlin-3-Mediated Cytotoxicity (Supplementry Table), Current Cancer Drug Targets 2009; 9 (4) . https://dx.doi.org/10.2174/156800909788486777
DOI https://dx.doi.org/10.2174/156800909788486777 |
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 Potential and Limitations of p38MAPK as a Drug Target for the Treatment of Hematological Malignancies
Current Drug Targets Potential Disease Targets for Drugs that Disrupt Protein - Protein Interactions of Grb2 and Crk Family Adaptors
Current Pharmaceutical Design Epidemiology of Candida albicans Infections and Role of Non-Candidaalbicans Yeasts
Current Drug Targets Contrast Enhanced Sonography for Diagnosis of (Peri-) Splenic Pathology
Current Medical Imaging A Review on Exploring Better Safety Prospects in Managing Cancer using Liposomal Combinations of Food Bioactive Compounds and Anticancer Drugs: Combisomes
Current Drug Delivery ANTI-ADHESION Evolves To a Promising Therapeutic Concept in Oncology
Current Medicinal Chemistry Application of Stem Cell Therapy During the Treatment of HIV/AIDS and Duchenne Muscular Dystrophy
Current Stem Cell Research & Therapy Enhancing Central Nervous System Endogenous GLP-1 Receptor Pathways for Intervention in Alzheimers Disease
Current Alzheimer Research Mevalonate Kinase Deficiency: Disclosing the Role of Mevalonate Pathway Modulation in Inflammation
Current Pharmaceutical Design A Dual Role for Sirtuin 1 in Tumorigenesis
Current Pharmaceutical Design Subcellular Trafficking in Rhabdovirus Infection and Immune Evasion: A Novel Target for Therapeutics
Infectious Disorders - Drug Targets Retroviral Gene Therapy: Safety Issues and Possible Solutions
Current Gene Therapy Novel Drug Therapies for Fertility Preservation in Men Undergoing Chemotherapy: Clinical Relevance of Protector Agents
Current Medicinal Chemistry Small Molecule Inhibitors of Protein Kinases in Cancer- How to Overcome Resistance
Mini-Reviews in Medicinal Chemistry The Development of Cytokine Receptor Antagonists as Potential Therapeutic Agents for the Myeloproliferative Disorders
Current Pharmaceutical Design RNA Silencing: Recent Developments on miRNAs
Recent Patents on DNA & Gene Sequences Barminomycin, a Model for the Development of New Anthracyclines
Anti-Cancer Agents in Medicinal Chemistry Gene Therapy Approaches for Neuroprotection and Axonal Regeneration after Spinal Cord and Spinal Root Injury
Current Gene Therapy Host Pharmacogenetics in the Treatment of HIV and Cancer
Current Drug Safety Cationicity and Hydrophobicity Enhance the Cytotoxic Potency of Phoratoxin C Anticancer Peptide Analogues against Triple Negative Breast Cancer Cells
Current Bioactive Compounds