In 1964, a new herpesvirus, Epstein-Barr virus (EBV), was discovered in cultured tumor cells derived from a Burkitt lymphoma (BL) biopsy taken from an African patient. This was a momentous event that reinvigorated research into viruses as a possible cause of human cancers. Subsequent studies demonstrated that EBV was a potent growth-transforming agent for primary B cells, and that all cases of BL carried characteristic chromosomal translocations resulting in constitutive activation of the c-MYC oncogene. These results hinted at simple oncogenic mechanisms that would make Burkitt lymphoma paradigmatic for cancers with viral etiology. In reality, the pathogenesis of this tumor is rather complicated with regard to both the contribution of the virus and the involvement of cellular oncogenes. Here, we review the current understanding of the roles of EBV and c-MYC in the pathogenesis of BL and the implications for new therapeutic strategies to treat this lymphoma.
B-Lymphocytes ; Burkitt Lymphoma ; virology ; Herpesvirus 4, Human ; Humans ; Translocation, Genetic

EBV (Epstein-Barr Virus) is a common herpes virus in patient with lymphatic system tumor, which firstly discovered in the cell line of Burkitt's lymphoma. 90% people worldwide had been infected by EB virus before grown-up, but not all people have the EBV-related disease or tumor. Most EBV infection can not elicit clinical symptoms. EBV infection in tumor of lymphatic system is common. It was early known that the EBV existence may cause the immortalization of normal B cells, which like the tumor cells. It means that EBV plays an important role in the tumorigenesis. EBV Bcrf1 code frame is homology to human IL-10, which is also called viral IL-10, showing immunosuppressive effect similar to the IL-10. IL-10 is also an important immunoregulatory factor, the secretory level of which influences the occurrence and development of lymphatic system diseases; the genotype of SNP site in IL-10 promoter region also associates with secretory level of IL-10. This review discusses the close relation between tumor of lymphatic system, EBV infection and gene polymorphism of IL-10.
Burkitt Lymphoma ; genetics ; virology ; Herpesvirus 4, Human ; genetics ; pathogenicity ; Humans ; Interleukin-10 ; genetics ; Lymphoma ; genetics ; virology ; Polymorphism, Single Nucleotide ; Viral Matrix Proteins ; genetics

Burkitt Lymphoma ; pathology ; virology ; Epstein-Barr Virus Infections ; pathology ; Hematologic Diseases ; pathology ; Histiocytic Necrotizing Lymphadenitis ; pathology ; Hodgkin Disease ; pathology ; Humans ; Lymphoma ; classification ; pathology

OBJECTIVE: To identify the Epstein-Barr virus (EBV) chromosomal integration sites in Raji cells. METHODS: EBV DNA was detected by Southern hybridization, and the viral chromosomal integration sites were identified using G banding and fluorescence in situ hybridization (FISH). RESULTS: BamHI-digested genomic DNA from Raji cells was hybridized with (32)P-labeled probe-1 (EBV genome 13,232 approximately 16,189) and Probe-2 (EBV genome 5 approximately 3,271), which generated 4 and 10, 23 kb positive bands respectively. The viral integration sites included 1p, 1q, 2q, 3p, 3q, 4 q, 5q, 6q, 7p, 7q, 9q,11p, 14 q, and 15q,and chromosomal bands 4 q, 2q, 1q and 7q were viral integration sites with high frequencies. Among the 33 signals counted, 7, 4, 4,and 4 signals were at the site 4 q, 2q, 1q, and 7q respectively, and 64% of the total signals were found in these 4 chromosomal bands. No viral integration occurred in chromosomes 16 approximately 22 or the sex chromosomes (X, Y). CONCLUSION This study firstly identifies the EBV integration sites in Raji cells using G banding and FISH. There are some viral integration sites with high frequencies in Raji cells, and EBV integrates into Raji cell genomes non-randomly.
Burkitt Lymphoma ; genetics ; pathology ; virology ; Cell Line, Tumor ; Chromosomes, Human, Pair 1 ; virology ; Chromosomes, Human, Pair 2 ; virology ; Chromosomes, Human, Pair 4 ; virology ; DNA, Viral ; genetics ; Genome, Viral ; Herpesvirus 4, Human ; genetics ; Humans ; In Situ Hybridization, Fluorescence ; Virus Integration ; genetics

This brief communication focuses on aspects of a recent case report (Yonsei Med J 2005;46:425-30) on a full and sustained remission of Hodgkin's lymphoma (HL) after a single day of chemotherapy. A septic episode required stopping chemotherapy and starting amphotericin B and acyclovir. Remission evidence was seen within days of starting these. A review of research supporting the notion that amphotericin B can reactivate latent Epstein-Barr virus and thus allow acyclovir to kill infected HL cells is given. Experimental work is required to confirm or refute this possibility. If successful, amphotericin B and acyclovir treatment could be extended to other EBV-driven cancers such as Burkitt's lymphoma, nasopharyngeal carcinoma and the occasional EBV-related epithelial cancer of the breast, colon, prostate, and others.
Virus Activation ; Tumor Necrosis Factor-alpha/metabolism ; Remission Induction ; Humans ; Hodgkin Disease/*drug therapy/pathology/*virology ; Herpesvirus 4, Human/*metabolism ; Ganciclovir/therapeutic use ; *Drug Synergism ; Burkitt Lymphoma/virology ; Anti-Bacterial Agents/pharmacology ; Amphotericin B/*pharmacology ; Acyclovir/*therapeutic use

Acquired Immunodeficiency Syndrome ; drug therapy ; genetics ; surgery ; Adult ; Burkitt Lymphoma ; drug therapy ; genetics ; surgery ; virology ; Diagnosis, Differential ; Female ; Genes, myc ; HIV ; isolation & purification ; HIV Infections ; Herpesvirus 4, Human ; genetics ; Humans ; Immunohistochemistry ; Lymphoma, AIDS-Related ; drug therapy ; genetics ; surgery ; virology ; Lymphoma, B-Cell ; pathology ; Lymphoma, Mantle-Cell ; pathology ; Male ; Middle Aged ; RNA, Viral ; analysis ; Sarcoma, Myeloid ; pathology ; Translocation, Genetic

OBJECTIVETo investigate the differential expression pattern of hsa-miR-9 between EBV-positive and -negative Burkitt lymphoma cell lines and its association with BCL-6.

METHODSThe expression of hsa-miR9 and BCL-6 mRNAs in EBV(+) Raji and EBV-Ramous cells in mRNA levels were detected using fluorescence quantitative PCR (QRT-PCR). The two cells lines were transiently transfected with hsa-mir9-inhibitor and hsa-mir9-minicsvia Oligofectamine 2000, and the changes in BCL6 expressions was detected using QRT-PCR and Western blotting. Annexin V/PI staining was used to analyze the apoptosis and morphological changes of the transfected cells.

RESULTSThe expression of Hsa-miR9 and BCL-6 was significantly higher in EBV(+) Raji cells than EBV(-) Ramous cells (P<0.01). BCL-6 mRNA and protein expression was reduced in EBV(+) Raji cells after transfection with hsa-miR9-inhibitor but up-regulated in EBV(-) Ramous cells transfected with hsa-miR9-minics. Flow cytometry revealed a significantly decreased apoptosis rate in EBV(+) Raji cells transfected with hsa-miR9-inhibitor but an increased rate in EBV(-) Ramous cells transfected with hsa-miR9-minics, and the results were confirmed by microscopic observations.

CONCLUSIONHsa-miR9 positively regulate the expression of BCL-6 and apoptosis of EBV(+) Raji cells and EBV(-) Ramous cells.

Apoptosis ; Burkitt Lymphoma ; genetics ; pathology ; virology ; Cell Division ; Cell Line, Tumor ; DNA-Binding Proteins ; genetics ; metabolism ; Gene Expression Regulation, Neoplastic ; Herpesvirus 4, Human ; Humans ; MicroRNAs ; metabolism ; Proto-Oncogene Proteins c-bcl-6 ; Transfection

OBJECTIVE: To construct the genomic library of Raji cells and screen it by EBV DNA probe. METHODS: High molecular weight genomic DNA of Raji cells was digested by restriction enzyme BamHI. DNA fragments ranging from 9 to 23 kb were recovered by agarose gel electrophoresis, which were ligated with Lambda DASH II vector BamHI arms pre-treated with calf intestine alkaline phosphatase (CIAP). Ligated DNA was packed in vitro using Gigapack III gold packaging extract. The library was plated on XL1-blue MRA (P2) host strain.Titering and screening of the Raji genomic library were performed. RESULTS: The primary titer of the Raji genomic library was 1.8 x 10(5) pfu/mL, while that of the amplified library was 2.8 x 10(8) pfu/mL. Plaques (1 x 10(5)) were screened with (32)P-labeled EBV DNA probe(EBV genome 5-3271), 4 positive clones were obtained, and 1 of the 4 positive clones was picked out randomly for the second round of plaque screening. All the phage plaques were positive. DNA of the positive clone was extracted and was digested with BamHI. The length of the inserted fragment was 8.5 kb. Sequencing and BLAST analysis revealed that the inserted fragments consisted of the BamHI-W fragment at one end and clone RP11-665A22 on chromosome 15 at the other end. CONCLUSION The successfully established genomic library of Raji cells will provide a basis for cloning the sequences of the EBV junction sites and interpreting the mechanism of oncogenesis of EBV integration.
Base Sequence ; Burkitt Lymphoma ; genetics ; virology ; Chromosomes, Human, Pair 15 ; genetics ; Cloning, Molecular ; DNA Probes ; genetics ; DNA, Viral ; genetics ; Gene Expression Profiling ; Genes, Neoplasm ; genetics ; Genomic Library ; Herpesvirus 4, Human ; genetics ; Humans ; Molecular Sequence Data ; Tumor Cells, Cultured