Rearrangements of the BCL-6 gene in acquired immunodeficiency syndrome- associated non-Hodgkin's lymphoma: Association with diffuse large-cell subtype

G. Gaidano, F. L. Coco, B. H. Ye, D. Shibata, A. M. Levine, D. M. Knowles, R. Dalla- Favera

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111 Scopus citations

Abstract

Acquired immunodeficiency syndrome (AIDS)-associated non-Hodgkin's lymphomas (AIDS-NHL), a major source of morbidity and mortality among AIDS patients, are derived from B cells and can be classified into two main histologic categories, small noncleaved cell lymphoma (SNCCL) and diffuse large-cell lymphoma (DLCL). DLCL includes two histologic subsets, ie, large noncleaved cell lymphoma (LNCCL) and large cell-immunoblastic plasmacytoid lymphoma (LC-IBPL). Several studies have shown that AIDS-SNCCL is associated with the clonal accumulation of multiple genetic lesions, including Epstein- Barr virus (EBV) infection, activation of the c-MYC and RAS oncogenes, as well as inactivation of the p53 tumor suppressor gene at variable frequencies. On the contrary, the molecular pathogenesis of AIDS-DLCL is largely obscure, because no genetic lesion other than EBV infection has been specifically identified in this group. In this study, we have tested a panel of 40 AIDS-NHL for structural alterations of BCL-6, a putative proto-oncogene that is frequently altered in DLCL in the immunocompetent host. Our results show that rearrangements of BCL-6 are present in 20% of AIDS-DLCL (5 of 24), including 2 of 8 LNCCL and 3 of 16 LC-IBPL, but in no case of AIDS-SNCCL. BCL-6 rearrangements were detected both in the presence and in the absence of EBV infection of the tumor clone, but in no case were associated with activation of c-MYC or mutations of p53. These data identify a novel genetic lesion in AIDS-DLCL and corroborate the notion that lymphomagenesis in AIDS follows two distinct molecular pathways that are associated with the development of histologically distinct types of AIDS-NHL.

Original languageEnglish (US)
Pages (from-to)397-402
Number of pages6
JournalBlood
Volume84
Issue number2
StatePublished - Jan 1 1994
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Gaidano, G., Coco, F. L., Ye, B. H., Shibata, D., Levine, A. M., Knowles, D. M., & Dalla- Favera, R. (1994). Rearrangements of the BCL-6 gene in acquired immunodeficiency syndrome- associated non-Hodgkin's lymphoma: Association with diffuse large-cell subtype. Blood, 84(2), 397-402.