Follicle center lymphoma is associated with significantly elevated levels of BCL-6 expression among lymphoma subtypes, independent of chromosome 3q27 rearrangements.

Abstract

The BCL-6 gene, located on chromosome 3q27, is implicated in the normal germinal center formation and is frequently rearranged in a wide spectrum of lymphomas. However the links between genetic alterations and expression of the gene are not clearly determined. We established a quantitative RT-PCR assay based on TaqMan technology to quantify BCL-6 mRNA expression in different subtypes of lymphomas and to compare the level of expression in lymphomas characterized by the presence or absence of BCL-6 translocation. Total RNA was extracted from 105 nodes biopsies (35 diffuse large B cell lymphomas (DLBCL); 26 follicle center lymphomas (FCL); 7 marginal zone lymphomas (MZL); 6 mantle cell lymphomas (MCL); 6 chronic lymphocytic leukemia (CLL); 5 T cell lymphomas (TCL); 7 classical Hodgkin diseases (HD); 6 nodal metastasis (NM); and 7 reactive hyperplasia (RH)). BCL-6 gene rearrangement was assessed by Southern blot analysis in 75% of 3q27(+) DLBCL (n = 20) cases and 67% of 3q27(+) cases (n = 10). The highest level of relative BCL-6 expression was observed in FCL (9.12 +/- 7.28) comparatively to the other lymphoma subtypes including DLBCL (2.53 +/- 1.82; P < 0.001), MCL (1.23 +/- 0.73), MZL (1.49 +/- 1.3), HD (1.60 +/- 1.00), TCL (1.75 +/- 1.64), but also RH (3.91 +/- 3.12) or NM (1.95 +/- 2.6). Among the 26 FCL cases, we observed a lower expression in grade 3 (n = 8) than in grade 1/2 (P < 0.001). Conversely, we failed to show any difference between 3q27(+) DLBCL and 3q27(-)DLBCL cases (P = 0.42). Paradoxically BCL-6 expression in 3q27(+) FCL (n = 10) was significantly lower than in 3q27(-) FCL cases (P = 0.035). Finally, this study showed that BCL-6 expression in lymphoma is largely independent of chromosome 3q27 rearrangement and is more related to the histological subtype. Clinical implication and alternative deregulation pathways of BCL-6 expression remain to be determined.

• Authors: F Jardin, G Buchonnet, F Parmentier, N Contentin, S Leprêtre, P Lenain, J M Picquenot, S Laberge, P Bertrand, A Stamatoullas, J D'Anjou, H Tilly, C Bastard
• Journal: Leukemia (Leukemia) Vol. 16 Issue 11 Pg. 2318-25 (Nov 2002) ISSN: 0887-6924 [Print] England
• PMID: 12399978 (Publication Type: Journal Article)

Chemical References

• DNA Primers
• DNA-Binding Proteins
• Proto-Oncogene Proteins
• Proto-Oncogene Proteins c-bcl-6
• RNA, Messenger
• RNA, Neoplasm
• Transcription Factors

Topics

• Biopsy
• Blotting, Southern
• Chromosome Aberrations
• Chromosomes, Human, Pair 3 (genetics)
• DNA Primers (chemistry)
• DNA-Binding Proteins (genetics, metabolism)
• Gene Expression Regulation, Leukemic (genetics)
• Gene Rearrangement
• Hodgkin Disease (genetics, metabolism)
• Humans
• Leukemia, Lymphocytic, Chronic, B-Cell (genetics, metabolism)
• Lymph Nodes (metabolism)
• Lymphoma, Follicular (genetics, metabolism)
• Lymphoma, Mantle-Cell (genetics, metabolism)
• Proto-Oncogene Proteins (genetics, metabolism)
• Proto-Oncogene Proteins c-bcl-6
• RNA, Messenger (metabolism)
• RNA, Neoplasm (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Transcription Factors (genetics, metabolism)
• Translocation, Genetic
• Tumor Cells, Cultured (pathology)
• Up-Regulation