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

Gianluca Gaidano, Francesco Lo Coco, B. Hilda Ye, Darryl Shibata, Alexandra M. Levine, Daniel M. Knowles, Riccardo Dalla-Favera

Research output: Contribution to journalArticle

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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 - Jul 15 1994
Externally publishedYes

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Viruses
Non-Hodgkin's Lymphoma
Acquired Immunodeficiency Syndrome
Genes
Lymphoma, Large B-Cell, Diffuse
Tumors
Chemical activation
Large-Cell Immunoblastic Lymphoma
Epstein-Barr Virus Infections
Cells
Virus Activation
Proto-Oncogenes
Tumor Suppressor Genes
Oncogenes
Lymphoma
B-Lymphocytes
Clone Cells
Morbidity
Mutation
Mortality

ASJC Scopus subject areas

  • Hematology

Cite this

Gaidano, G., Lo Coco, F., 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.

Rearrangements of the BCL-6 gene in acquired immunodeficiency syndrome-associated non-Hodgkin's lymphoma : Association with diffuse large-cell subtype. / Gaidano, Gianluca; Lo Coco, Francesco; Ye, B. Hilda; Shibata, Darryl; Levine, Alexandra M.; Knowles, Daniel M.; Dalla-Favera, Riccardo.

In: Blood, Vol. 84, No. 2, 15.07.1994, p. 397-402.

Research output: Contribution to journalArticle

Gaidano, G, Lo Coco, F, Ye, BH, Shibata, D, Levine, AM, Knowles, DM & 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, vol. 84, no. 2, pp. 397-402.
Gaidano, Gianluca ; Lo Coco, Francesco ; Ye, B. Hilda ; Shibata, Darryl ; Levine, Alexandra M. ; Knowles, Daniel M. ; Dalla-Favera, Riccardo. / Rearrangements of the BCL-6 gene in acquired immunodeficiency syndrome-associated non-Hodgkin's lymphoma : Association with diffuse large-cell subtype. In: Blood. 1994 ; Vol. 84, No. 2. pp. 397-402.
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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.",
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AU - Ye, B. Hilda

AU - Shibata, Darryl

AU - Levine, Alexandra M.

AU - Knowles, Daniel M.

AU - Dalla-Favera, Riccardo

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N2 - 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.

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