The BCL-6 gene encoding a nuclear-located Kruppel-type zinc finger protein is rearranged in about 30% diffuse large B-cell lymphomas and is expressed predominantly in normal germinal center B cells and related lymphomas. These findings suggest that BCL-6 may play a role in regulating differentiation of normal germinal center B cells and that its deregulated expression caused by rearrangements may contribute to lymphomagenesis. This prompted us to investigate the expression of the BCL-6 protein in Hodgkin's disease (HD), focusing on the nodular lymphocyte predominance subtype (NLPHD), which differs from classical HD by virtue of the B-cell nature of the malignant cell population (so-called L&H cells) and its relationship with germinal centers. Forty-one HD samples (19 NLPHD, 12 nodular sclerosis, and 10 mixed cellularity) were immunostained with the monoclonal antibodies PG-B6 and PG-B6p that react with a fixative-sensitive and a formalin-resistant epitope on the aminoterminal region of the BCL-6 gene product, respectively. Strong nuclear positivity for the BCL-6 protein was detected in tumor (L&H) cells in all cases of NLPHD. In contrast, BCL-6 was expressed only in a small percentage of Hodgkin and Reed-Sternberg cells in about 30% of classical HD cases. Notably, the nuclei of reactive CD3+/CD4+ T cells nearby to and rosetting around L&H cells in NLPHD were also strongly BCL-6+, but lacked CD40 ligand (CD40L) expression. This staining pattern clearly differed from that of classical HD, whose cellular background was made up of CD3+/CD4+ T cells showing the BCL-6-/CD40L+ phenotype. These results further support the concept that NLPHD is an histogenetically distinct, B-cell-derived subtype of HD and suggest a role for BCL-6 in its development.

Distinctive expression pattern of the BCL-6 protein in nodular lymphocyte predominance Hodgkin's disease / B. Falini, B. Bigerna, L. Pasqualucci, M. Fizzotti, M. F. Martelli, S. Pileri, A. Pinto, A. Carbone, S. Venturi, R. Pacini, G. Cattoretti, E. Pescarmona, F. Lo Coco, P. G. Pelicci, I. Anagnastopoulos, R. Dalla-Favera, L. Flenghi. - In: BLOOD. - ISSN 0006-4971. - 87:2(1996 Jan 15), pp. 465-71-471.

Distinctive expression pattern of the BCL-6 protein in nodular lymphocyte predominance Hodgkin's disease

P. G. Pelicci;
1996

Abstract

The BCL-6 gene encoding a nuclear-located Kruppel-type zinc finger protein is rearranged in about 30% diffuse large B-cell lymphomas and is expressed predominantly in normal germinal center B cells and related lymphomas. These findings suggest that BCL-6 may play a role in regulating differentiation of normal germinal center B cells and that its deregulated expression caused by rearrangements may contribute to lymphomagenesis. This prompted us to investigate the expression of the BCL-6 protein in Hodgkin's disease (HD), focusing on the nodular lymphocyte predominance subtype (NLPHD), which differs from classical HD by virtue of the B-cell nature of the malignant cell population (so-called L&H cells) and its relationship with germinal centers. Forty-one HD samples (19 NLPHD, 12 nodular sclerosis, and 10 mixed cellularity) were immunostained with the monoclonal antibodies PG-B6 and PG-B6p that react with a fixative-sensitive and a formalin-resistant epitope on the aminoterminal region of the BCL-6 gene product, respectively. Strong nuclear positivity for the BCL-6 protein was detected in tumor (L&H) cells in all cases of NLPHD. In contrast, BCL-6 was expressed only in a small percentage of Hodgkin and Reed-Sternberg cells in about 30% of classical HD cases. Notably, the nuclei of reactive CD3+/CD4+ T cells nearby to and rosetting around L&H cells in NLPHD were also strongly BCL-6+, but lacked CD40 ligand (CD40L) expression. This staining pattern clearly differed from that of classical HD, whose cellular background was made up of CD3+/CD4+ T cells showing the BCL-6-/CD40L+ phenotype. These results further support the concept that NLPHD is an histogenetically distinct, B-cell-derived subtype of HD and suggest a role for BCL-6 in its development.
Animals; Membrane Glycoproteins; Humans; B-Lymphocytes; Mice, Inbred BALB C; Reed-Sternberg Cells; Lymphocytes, Tumor-Infiltrating; CD40 Ligand; Antibodies, Monoclonal; Gene Expression Regulation, Neoplastic; Transcription Factors; Proto-Oncogene Proteins c-bcl-6; Hodgkin Disease; Tumor Markers, Biological; Embryonal Carcinoma Stem Cells; Neoplastic Stem Cells; DNA-Binding Proteins; Antigens, Neoplasm; Mice; Neoplasm Proteins; Proto-Oncogene Proteins; Antigens, CD3; Antigens, CD4; Rosette Formation; T-Lymphocyte Subsets
Settore MED/04 - Patologia Generale
15-gen-1996
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/195575
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