BCL-6 protein expression in AIDS-related non-Hodgkin's lymphomas: inverse relationship with Epstein-Barr virus-encoded latent membrane protein-1 expression.
This study aimed at investigating the expression of the BCL-6 protein in acquired immune deficiency syndrome (AIDS)-related non-Hodgkin's lymphomas (AIDS-NHLs) and at comparing the expression pattern with the presence of Epstein-Barr virus (EBV) infection of the tumor clone. A total of 34 AIDS-NHL biopsies, including 16 AIDS-related diffuse large-cell lymphomas (AIDS-DLCLs) and 18 AIDS-related small-noncleaved-cell lymphomas (AIDS-SNCCLs) as well as 7 AIDS-SNCCL cell lines were immunostained with a BCL-6-specific monoclonal antibody. Expression of BCL-6 protein was detected in 9 of 16 AIDS-DLCLs, 18 of 18 AIDS-SNCCLs, and 3 of 7 AIDS-SNCCL cell lines. Expression of BCL-6 among AIDS-NHLs occurred independently of the presence of molecular lesions of the bcl-6 gene. Notably, among EBV-positive AIDS-NHL biopsies and cell lines, expression of BCL-6 was mutually exclusive with the expression of EBV-encoded transforming antigen latent membrane protein-1. The mutual exclusion between BCL-6 and latent membrane protein-1 expression was further confirmed by in vitro superinfection experiments of an AIDS-SNCCL cell line originally devoid of EBV sequences. Overall, the frequent association between AIDS-NHLs and expression of BCL-6, a protein selectively expressed by germinal center B cells, suggests that these lymphomas may originate from the germinal center.
Carbone
A
A
Division of Pathology, Istituto Nazionale di Ricovero e Cura a Carattere Scientifico, Aviano, Italy.
Gaidano
G
G
Gloghini
A
A
Pastore
C
C
Saglio
G
G
Tirelli
U
U
Dalla-Favera
R
R
Falini
B
B
D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002460:Cell Line; D002869:Chromosome Aberrations / Q000473:pathology; D025063:Chromosome Disorders; D002893:Chromosomes, Human, Pair 3; D002898:Chromosomes, Human, Pair 8; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D019309:Epstein-Barr Virus Nuclear Antigens / Q000096:biosynthesis; D016259:Genes, myc; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000737:chemistry / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis* / Q000235:genetics; D017354:Point Mutation; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D014763:Viral Matrix Proteins / Q000096:biosynthesis*
D004268:DNA-Binding Proteins; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; D009856:Oncogene Proteins, Viral; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors; D014763:Viral Matrix Proteins