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.

Falini, B., Bigerna, B., Pasqualucci, L., Fizzotti, M., Martelli, M.f., Pileri, S., et al. (1996). Distinctive expression pattern of the BCL-6 protein in nodular lymphocyte predominance Hodgkin's disease. BLOOD, 87(2), 465-471.

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

LO COCO, FRANCESCO;
1996-01-15

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.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/15 - Malattie del Sangue
English
Animals; Antibodies, Monoclonal; Antigens, CD3; Antigens, CD4; Antigens, Neoplasm; B-Lymphocytes; Biomarkers, Tumor; CD40 Ligand; DNA-Binding Proteins; Embryonal Carcinoma Stem Cells; Hodgkin Disease; Humans; Lymphocytes, Tumor-Infiltrating; Membrane Glycoproteins; Mice; Mice, Inbred BALB C; Neoplasm Proteins; Neoplastic Stem Cells; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-6; Reed-Sternberg Cells; Rosette Formation; T-Lymphocyte Subsets; Transcription Factors; Gene Expression Regulation, Neoplastic
Falini, B., Bigerna, B., Pasqualucci, L., Fizzotti, M., Martelli, M.f., Pileri, S., et al. (1996). Distinctive expression pattern of the BCL-6 protein in nodular lymphocyte predominance Hodgkin's disease. BLOOD, 87(2), 465-471.
Falini, B; Bigerna, B; Pasqualucci, L; Fizzotti, M; Martelli, M; Pileri, S; Pinto, A; Carbone, A; Venturi, S; Pacini, R; Cattoretti, G; Pescarmona, E; LO COCO, F; Pelicci, P; Anagnastopoulos, I; Dalla Favera, R; Flenghi, L
Articolo su rivista
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/161718
Citazioni
  • ???jsp.display-item.citation.pmc??? 12
  • Scopus 93
  • ???jsp.display-item.citation.isi??? ND
social impact