Burkitt Lymphoma: Revisiting the Pathogenesis of a Virus-Associated Malignancy

Hematology ◽  
2007 ◽  
Vol 2007 (1) ◽  
pp. 277-284 ◽  
Author(s):  
Gemma L. Kelly ◽  
Alan B. Rickinson
Keyword(s):  
Burkitt Lymphoma ◽  
Chromosomal Translocation ◽  
Genetic Changes ◽  
Myc Oncogene ◽  
Barr Virus ◽  
Additional Protection ◽  
Associated Malignancy ◽  
Epstein Barr ◽  
The Many ◽  
Apoptotic Effects

AbstractBurkitt lymphoma (BL), a tumor occurring in endemic, sporadic and AIDS-associated forms, is the classic example of a human malignancy whose pathogenesis involves a specific cellular genetic change, namely, a chromosomal translocation deregulating expression of the c-myc oncogene, complemented in many cases by the action of an oncogenic virus, the Epstein-Barr virus (EBV). Here we review recent work in two complementary areas of research: (1) on cellular genetic changes that occur in addition to the c-myc translocation in BL, in particular the capacity of p53/ ARF pathway breakage or of c-myc mutation to decouple the pro-proliferative effects of c-myc deregulation from its pro-apoptotic effects; and (2) on a postulated role for EBV in BL pathogenesis, through adopting restricted forms of virus latent gene expression that remain compatible with the c-myc–driven growth program but offer the tumor additional protection from apoptosis. We stress the many fundamental questions that remain to be resolved and, in that regard, highlight the general lessons that might be learned through understanding how two other infectious agents, malaria and HIV, dramatically enhance BL incidence.

scholarly journals EBV Reactivation and Chromosomal Polysomies:Euphorbia tirucallias a Possible Cofactor in Endemic Burkitt Lymphoma

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Susanna Mannucci ◽  
Anna Luzzi ◽  
Alessandro Carugi ◽  
Alessandro Gozzetti ◽  
Stefano Lazzi ◽  
...  
Keyword(s):  
Burkitt Lymphoma ◽  
Herbal Remedy ◽  
Chromosomal Translocation ◽  
Herbal Remedies ◽  
Altered Expression ◽  
Barr Virus ◽  
Ebv Reactivation ◽  
Euphorbia Tirucalli ◽  
Equatorial Belt ◽  
Epstein Barr

Burkitt lymphoma is endemic in the Equatorial Belt of Africa, its molecular hallmark is an activated,MYCgene mostly due to a chromosomal translocation. Especially in its endemic clinical variant, Burkitt lymphoma is associated with the oncogenic Epstein-Barr virus (EBV), and holoendemic malaria acts as an amplifier. Environmental factors may also cooperate in Burkitt lymphomagenesis in the endemic regions, such as plants used as traditional herbal remedies.Euphorbia tirucalli, a plant known to possess EBV-activating substances, has a similar geographical distribution to endemic Burkitt’s Lymphoma and is used as a hedge, herbal remedy and toy in the Lymphoma BeltI. In this study we aimed at determining if exposure toEuphorbia tirucallicould contribute to lymphomagenesis, and at which extent. Lymphoblastoid and cord blood-derived cell lines were treated with plant extracts, and the expression of EBV-coded proteins was checked, to assess EBV reactivation. The occurrence of chromosomal translocations was then investigated by FISH. Our preliminary results suggest thatE. tirucalliis able to reactivate EBV and determine chromosomal alterations, which leads to c-MYC altered expression. The existence of genomic alterations might determine the accumulation of further genetic alteration, which could eventually lead to a transformed phenotype.

scholarly journals Three Restricted Forms of Epstein-Barr Virus Latency Counteracting Apoptosis in c-Myc Expressing Burkitt Lymphoma Cells.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1572-1572 ◽  
Author(s):  
Gemma L. Kelly ◽  
Julianna Stylianou ◽  
Andrew I. Bell ◽  
Wenbin Wei ◽  
Martin Rowe ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Microarray Analysis ◽  
Burkitt Lymphoma ◽  
Epstein Barr Virus ◽  
Chromosomal Translocation ◽  
Cell System ◽  
Virus Growth ◽  
Barr Virus ◽  
Epstein Barr

Abstract Epstein-Barr virus (EBV) is aetiologically linked with Burkitt Lymphoma (BL) but its contribution to lymphomagenesis, versus that of the chromosomal translocation activating c-myc expression, remains unclear. This is in part because the full virus growth transforming programme that is expressed when EBV infects normal resting B cells, is not expressed in BL. Instead EBV in BL normally exhibits a restricted Latency I form of infection characterised by expression of only one latent antigen EBNA1 from the BamHI Q promoter. Here we describe an endemic BL, Awia, which uniquely is heterogeneous at the single cell level for EBV gene expression. Analysis of single cell clones of Awia-BL revealed cells displaying three forms of restricted EBV latency: classical Latency I, ’Wp-restricted latency’ expressing EBNAs 1, 3A, 3B, 3C and -LP, and a novel ’EBNA2+/LMP1- latency’ in which all EBNAs including EBNA2 are expressed without the latent membrane proteins LMPs 1 and 2. Comparison with rare EBV-negative clones from the same tumour showed that each form of infection provides the c-myc-expressing BL cells with a specific degree of protection from apoptosis. Microarray analysis was carried out on the isogenic Awia-BL clones to determine the influence of EBV gene expression on cellular transcription. Interestingly it was found that expression of the pro-apoptotic Bcl2 family protein BIM, which has previously been implicated in c-myc induced apoptosis, was downregulated in the apoptosis resistant BL cells. Our work suggests that EBV acts as an anti-apoptotic rather than a growth-promoting agent in BL by downregulating expression of the cellular BIM protein. In addition the microarray analysis on these isogenic Awia-BL clones showed that the EBNA profile influences the differentiation status of the BL cell on the germinal centre to plasmacytoid differentiation pathway. These findings may reflect viral functions that are important not just for BL pathogenesis but also for EBV’s normal strategy of persistence in the B cell system.

scholarly journals Molecular Genetics in Epstein–Barr Virus-Associated Malignancies

Life ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 593
Author(s):  
Srikanth Umakanthan ◽  
Maryann M Bukelo
Keyword(s):  
Epstein Barr Virus ◽  
Diagnostic Tools ◽  
Main Role ◽  
Genetic Changes ◽  
Barr Virus ◽  
Cancer Pathogenesis ◽  
Genomic Studies ◽  
Epstein Barr ◽  
Oncogenic Form

Global genomic studies have detected the role of genomic alterations in the pathogenesis of Epstein–Barr virus (EBV)-associated tumors. EBV oncoproteins cause a vital shift of EBV from an infectious virus to an oncogenic form during the latent and lytic phase within the lymphoid B cells and epithelial cells. This epigenetic alteration modulates the virus and host genomes and inactivates and disrupts numerous tumor suppressors and signaling pathways. Genomic profiling has played the main role in identifying EBV cancer pathogenesis and its related targeted therapies. This article reviews the role of genetic changes in EBV-associated lymphomas and carcinomas. This includes the prolific molecular genesis, key diagnostic tools, and target-specific drugs that have been in recent clinical use.

scholarly journals Epstein Barr virus genomes reveal population structure and type 1 association with endemic Burkitt lymphoma

2019 ◽  
Author(s):  
Yasin Kaymaz ◽  
Cliff I. Oduor ◽  
Ozkan Aydemir ◽  
Micah A. Luftig ◽  
Juliana A. Otieno ◽  
...  
Keyword(s):  
Population Structure ◽  
Burkitt Lymphoma ◽  
Epstein Barr Virus ◽  
Genome Wide Association ◽  
Viral Dna ◽  
Barr Virus ◽  
Genome Wide ◽  
Epstein Barr

AbstractEndemic Burkitt lymphoma (eBL), the most prevalent pediatric cancer in sub-Saharan Africa, is associated with malaria and Epstein Barr virus (EBV). In order to better understand the role of EBV in eBL, we improved viral DNA enrichment methods and generated a total of 98 new EBV genomes from both eBL cases (N=58) and healthy controls (N=40) residing in the same geographic region in Kenya. Comparing cases and controls, we found that EBV type 1 was significantly associated with eBL with 74.5% of patients (41/55) versus 47.5% of healthy children (19/40) carrying type 1 (OR=3.24, 95% CI=1.36 - 7.71,P=0.007). Controlling for EBV type, we also performed a genome-wide association study identifying 6 nonsynonymous variants in the genes EBNA1, EBNA2, BcLF1, and BARF1 that were enriched in eBL patients. Additionally, we observed that viruses isolated from plasma of eBL patients were identical to their tumor counterpart consistent with circulating viral DNA originating from the tumor. We also detected three intertypic recombinants carrying type 1 EBNA2 and type 2 EBNA3 regions as well as one novel genome with a 20 kb deletion resulting in the loss of multiple lytic and virion genes. Comparing EBV types, genes show differential variation rates as type 1 appears to be more divergent. Besides, type 2 demonstrates novel substructures. Overall, our findings address the complexities of EBV population structure and provide new insight into viral variation, which has the potential to influence eBL oncogenesis.Key PointsEBV type 1 is more prevalent in eBL patients compared to the geographically matched healthy control group.Genome-wide association analysis between cases and controls identifies 6 eBL-associated nonsynonymous variants in EBNA1, EBNA2, BcLF1, and BARF1 genes.Analysis of population structure reveals that EBV type 2 exists as two genomic sub groups.

scholarly journals TCL1 Expression and Epstein-Barr Virus Status in Pediatric Burkitt Lymphoma

2005 ◽  
Vol 124 (4) ◽  
pp. 569-575 ◽  
Author(s):  
Michael A. Teitell ◽  
Mark A. Lones ◽  
Sherrie L. Perkins ◽  
Warren G. Sanger ◽  
Mitchell S. Cairo ◽  
...  
Keyword(s):  
Burkitt Lymphoma ◽  
Epstein Barr Virus ◽  
Barr Virus ◽  
Epstein Barr

scholarly journals Infection of Epstein–Barr Virus in Type III Latency Modulates Biogenesis of Exosomes and the Expression Profile of Exosomal miRNAs in the Burkitt Lymphoma Mutu Cell Lines

Cancers ◽  
2018 ◽  
Vol 10 (7) ◽  
pp. 237 ◽  
Author(s):  
Asuka Nanbo ◽  
Harutaka Katano ◽  
Michiyo Kataoka ◽  
Shiho Hoshina ◽  
Tsuyoshi Sekizuka ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Burkitt Lymphoma ◽  
Epstein Barr Virus ◽  
Type I ◽  
Type Iii ◽  
Barr Virus ◽  
Ebv Infection ◽  
Latently Infected ◽  
Infected Cells ◽  
Epstein Barr

Infection of Epstein–Barr virus (EBV), a ubiquitous human gamma herpesvirus, is associated with various malignancies in B lymphocytes and epithelial cells. EBV encodes 49 microRNAs in two separated regions, termed the BART and BHRF1 loci. Although accumulating evidence demonstrates that EBV infection regulates the profile of microRNAs in the cells, little is known about the microRNAs in exosomes released from infected cells. Here, we characterized the expression profile of intracellular and exosomal microRNAs in EBV-negative, and two related EBV-infected Burkitt lymphoma cell lines having type I and type III latency by next-generation sequencing. We found that the biogenesis of exosomes is upregulated in type III latently infected cells compared with EBV-negative and type I latently infected cells. We also observed that viral and several specific host microRNAs were predominantly incorporated in the exosomes released from the cells in type III latency. We confirmed that multiple viral microRNAs were transferred to the epithelial cells cocultured with EBV-infected B cells. Our findings indicate that EBV infection, in particular in type III latency, modulates the biogenesis of exosomes and the profile of exosomal microRNAs, potentially contributing to phenotypic changes in cells receiving these exosomes.

Department of Additional Information

1986 ◽  
Vol 7 (7) ◽  
pp. 222-222
Author(s):  
MARGARET A. KENNA
Keyword(s):  
Nasotracheal Intubation ◽  
Epstein Barr Virus Infection ◽  
Additional Information ◽  
Barr Virus ◽  
Nasopharyngeal Airway ◽  
Epstein Barr ◽  
Barr Virus Infection ◽  
The Many ◽  
Posterior Pharynx ◽  
Excellent Article

While reading the otherwise excellent article, "The Many Faces of Infectious Mononucleosis: The Spectrum of Epstein-Barr Virus Infection in Children" (Pediatrics in Review 1985;7:35-44), I noted that Dr Grose refers to the airway management of these children done at the Children's Hospital of Pittsburgh. Dr Snyderman's article to which Dr Grose refers (Pediatric Clinics of North America 1981;28:1011-1016), however, does not recommend nasotracheal intubation, as described by Dr Grose but, rather, placement of a nasopharyngeal airway. This tube does not enter the trachea between the vocal cords but, essentially, bypasses the enlarged adenoids and tonsils and rests in the posterior pharynx.

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