EBV and genomic instability—A new look at the role of the virus in the pathogenesis of Burkitt's lymphoma

2009 ◽  
Vol 19 (6) ◽  
pp. 394-400 ◽  
Author(s):  
Bettina Gruhne ◽  
Siamak Akbari Kamranvar ◽  
Maria G. Masucci ◽  
Ramakrishna Sompallae
Keyword(s):  
Genomic Instability ◽  
Burkitt’S Lymphoma ◽  
Burkitt's Lymphoma ◽  
New Look

scholarly journals Oncogenic Role of Epstein-Barr Virus-Encoded RNAs in Burkitt’s Lymphoma Cell Line Akata

1999 ◽  
Vol 73 (12) ◽  
pp. 9827-9831 ◽  
Author(s):  
Jun Komano ◽  
Seiji Maruo ◽  
Koichi Kurozumi ◽  
Takanori Oda ◽  
Kenzo Takada
Keyword(s):  
Cell Line ◽  
Small Rnas ◽  
Epstein Barr Virus ◽  
Burkitt’S Lymphoma ◽  
Soft Agar ◽  
Burkitt's Lymphoma ◽  
Malignant Phenotype ◽  
Barr Virus ◽  
Epstein Barr

ABSTRACT Our previous reports indicated that Epstein-Barr virus (EBV) contributes to the malignant phenotype and resistance to apoptosis in Burkitt’s lymphoma (BL) cell line Akata (N. Shimizu, A. Tanabe-Tochikura, Y. Kuroiwa, and K. Takada, J. Virol. 68:6069–6073, 1994; J. Komano, M. Sugiura, and K. Takada, J. Virol. 72:9150–9156, 1998). Here we report that the EBV-encoded small RNAs (EBERs) are responsible for these phenotypes. Transfection of the EBER genes into EBV-negative Akata clones restored the capacity for growth in soft agar, tumorigenicity in SCID mice, resistance to apoptotic inducers, and upregulated expression of bcl-2 oncoprotein that were originally retained in parental EBV-positive Akata cells and lost in EBV-negative subclones. This is the first report which provides evidence that virus-encoded RNAs (EBERs) have oncogenic functions in BL cells.

scholarly journals Differential role of FL-BID and t-BID during verotoxin-1-induced apoptosis in Burkitt’s lymphoma cells

Oncogene ◽  
2018 ◽  
Vol 37 (18) ◽  
pp. 2410-2421 ◽  
Author(s):  
Justine Debernardi ◽  
Emilie Hollville ◽  
Marc Lipinski ◽  
Joëlle Wiels ◽  
Aude Robert
Keyword(s):  
Burkitt’S Lymphoma ◽  
Burkitt's Lymphoma ◽  
Lymphoma Cells ◽  
Induced Apoptosis ◽  
Burkitt’S Lymphoma Cells

scholarly journals The Primary Outbreaks of Burkitt Lymphoma in the Oral Cavity. A Report of Two Cases, Review of the Literature and Dental Implications

Diagnostics ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 2358
Author(s):  
Tomasz Kulczyk ◽  
Agata Daktera-Micker ◽  
Barbara Biedziak ◽  
Agnieszka Wziątek ◽  
Katarzyna Bednarek-Rajewska
Keyword(s):  
Oral Cavity ◽  
Incidental Findings ◽  
Primary Care Physicians ◽  
Therapeutic Process ◽  
Burkitt’S Lymphoma ◽  
Diagnostic Methods ◽  
Burkitt's Lymphoma ◽  
Primary Reason ◽  
Review Of The Literature

Two cases of Sporadic Burkitt’s lymphoma in children aged 11 and 8 years with primary symptoms in the oral cavity are reported. The first symptoms of the disease appeared in the oral cavity and were initially misdiagnosed as an inflammatory condition in one case and incidental findings not associated with the primary reason for visiting the dentist’s office in the second case. Biopsies of the lesions revealed the actual cause of the observed changes and contributed to the prompt initiation of polychemotherapy treatment. A review of current literature presents the known symptoms of Burkitt’s Lymphoma in the oral cavity and the available diagnostic methods. The role of the primary care physicians—the pedodontist and paediatrician—in the diagnostic and therapeutic process is discussed.

Modeling Proteasome Inhibition in Lymphoma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4946-4946
Author(s):  
Linda B. Baughn ◽  
Holly Stessman ◽  
Aatif Mansoor ◽  
Brian Van Ness
Keyword(s):  
Drug Resistance ◽  
Genomic Instability ◽  
Proteasome Inhibitor ◽  
Research Funding ◽  
Proteasome Inhibitors ◽  
Fold Increase ◽  
Proteasome Inhibition ◽  
Burkitt’S Lymphoma ◽  
Model System ◽  
Burkitt's Lymphoma

Abstract Abstract 4946 The proteasome inhibitor Bortezomib (Bz) has been widely used to treat multiple myeloma, relapsed mantle cell lymphoma and is undergoing clinical evaluation for other B cell malignancies including non-Hodgkin lymphoma. Despite its initial success, patients treated with Bz eventually relapse due to the development of drug resistance. Therefore, understanding the basis of drug resistance is a critical component for improved therapy. The acquisition of Bz resistance in lymphomas, particularly those with constitutive expression of the B cell-specific DNA mutator, activation-induced cytidine deaminase (AID), has not been previously characterized. We have utilized the AID-expressing human non-Hodgkin Burkitt's lymphoma as a model system for this study. Burkitt's lymphoma lines (Ramos and BL-2) are suitable because they are highly sensitive to Bz induced apoptosis with an IC50 of approximately 11 nM after 48 hrs of treatment. In order to generate Bz resistant Burkitt's lymphoma lines, Ramos cells were treated weekly with increasing concentrations of Bz for 3 months. Compared to the parental line, this newly formed line displayed an approximately 2.5–3-fold increase in IC50 to Bz as well as to three other proteasome inhibitors (next-generation proteasome inhibitor, MLN 2238, epoxomicin and carfilzomib), while maintaining sensitivity to different chemotherapeutic agents (PD 0332991 cyclin 4/6 dependent kinase inhibitor and melphalan). In this model system, resistance to Bz conferred a general cross-resistance to other proteasome inhibitors, a phenotype that has been stably maintained for 5 months. We next asked whether AID plays a role in the acquisition of Bz resistance in Ramos cells by promoting hypermutation and genomic instability. In support of this hypothesis, the G322A and C326T mutations in the gene encoding the proteasome subunit and target of Bz, psmb5, occur within AID hotspots raising the possibility that AID could directly mutate psmb5. Furthermore, like many proteins, AID is degraded by the proteasome arguing that proteasome inhibition further stabilizes AID protein resulting in aberrant hypermutation. Consistent with this, we detected by flow cytometry (intracellular staining) a 2-fold increase in AID protein following a 24-hour, 20 nM Bz treatment of Ramos cells. AID normally mutates immunoglobulin (Ig) genes and these mutations are necessary for the production of protective antibodies, while aberrant AID activity leads to mutations in non-Ig genes. Surprisingly, despite the increase in AID protein, we observe reduced mutation frequency within the functional IgH gene following 3-month Bz treatment compared to untreated controls. Despite this reduction, array comparative genomic hybridization (a-CGH) studies indicate copy number abnormalities in Bz resistant cells and details of the chromosomal abnormalities and target genes deregulated will be presented. These data demonstrate that Burkitt's lymphoma cells are sensitive to Bz and drug resistance can be readily achieved in vitro. Furthermore, Bz treatment stabilizes AID protein and promotes increased genomic instability. Disclosures: Stessman: Millennium: The Takeda Oncology Company: Research Funding. Mansoor:Millennium: The Takeda Oncology Company: Research Funding. Van Ness:Millennium: The Takeda Oncology Company: Research Funding.

scholarly journals HMG-I/Y, a New c-Myc Target Gene and Potential Oncogene

2000 ◽  
Vol 20 (15) ◽  
pp. 5490-5502 ◽  
Author(s):  
Lisa J. Wood ◽  
Mita Mukherjee ◽  
Christine E. Dolde ◽  
Yi Xu ◽  
Joseph F. Maher ◽  
...  
Keyword(s):  
Target Gene ◽  
Cellular Proliferation ◽  
Neoplastic Transformation ◽  
Burkitt’S Lymphoma ◽  
Burkitt's Lymphoma ◽  
Protein Synthesis Inhibitor ◽  
Synthesis Inhibitor ◽  
Serum Stimulation

ABSTRACT The HMG-I/Y gene encodes the HMG-I and HMG-Y proteins, which function as architectural chromatin binding proteins important in the transcriptional regulation of several genes. Although increased expression of the HMG-I/Y proteins is associated with cellular proliferation, neoplastic transformation, and several human cancers, the role of these proteins in the pathogenesis of malignancy remains unclear. To better understand the role of these proteins in cell growth and transformation, we have been studying the regulation and function of HMG-I/Y. The HMG-I/Y promoter was cloned, sequenced, and subjected to mutagenesis analysis. A c-Myc–Max consensus DNA binding site was identified as an element important in the serum stimulation of HMG-I/Y. The oncoprotein c-Myc and its protein partner Max bind to this site in vitro and activate transcription in transfection experiments. HMG-I/Yexpression is stimulated by c-Myc in a Myc-estradiol receptor cell line in the presence of the protein synthesis inhibitor cycloheximide, indicating that HMG-I/Y is a direct c-Myc target gene.HMG-I/Y induction is decreased in Myc-deficient fibroblasts. HMG-I/Y protein expression is also increased in Burkitt's lymphoma cell lines, which are known to have increased c-Myc protein. Like Myc, increased expression of HMG-I protein leads to the neoplastic transformation of both Rat 1a fibroblasts and CB33 cells. In addition, Rat 1a cells overexpressing HMG-I protein form tumors in nude mice. Decreasing HMG-I/Y proteins using an antisense construct abrogates transformation in Burkitt's lymphoma cells. These findings indicate that HMG-I/Y is a c-Myc target gene involved in neoplastic transformation and a member of a new class of potential oncogenes.

scholarly journals Replacement of the Epstein-Barr Virus Plasmid with the EBER Plasmid in Burkitt's Lymphoma Cells

2001 ◽  
Vol 75 (20) ◽  
pp. 9977-9982 ◽  
Author(s):  
Seiji Maruo ◽  
Asuka Nanbo ◽  
Kenzo Takada
Keyword(s):  
Epstein Barr Virus ◽  
Burkitt’S Lymphoma ◽  
Burkitt's Lymphoma ◽  
Substantial Decrease ◽  
Lymphoma Cells ◽  
Barr Virus ◽  
Epstein Barr ◽  
Do So ◽  
Burkitt’S Lymphoma Cells

ABSTRACT Transfection of an Epstein-Barr virus (EBV)-encoded plasmid containing EBER caused a substantial decrease in the level of plasmid containing EBV in Akata and Mutu Burkitt's lymphoma (BL) lines, but failed to do so in other BL lines. The results suggest that EBER could replace the role of EBV, but other EBV products also play a role in the growth of BL.

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