title: Alterations on the 5' noncoding region of the BCL-6 gene are not correlated with BCL-6 protein expression in T cell non-Hodgkin lymphomas.
abstract: The BCL-6 proto-oncogene is expressed in germinal center B lymphocytes, in their neoplastic counterparts, and in a subpopulation of germinal center and perifollicular T lymphocytes. Rearrangements and/or mutations of the 5' noncoding region of the bcl-6 gene have been demonstrated in a large majority of diffuse large B cell lymphomas. Some, but not all, of these genetic alterations lead to dysregulation of the protein. Recently, anaplastic large cell lymphomas with T and null cell phenotypes, as well as T lymphoblastic lymphomas, have also been reported to exhibit immunoreactivity to the anti-BCL-6 antibody. We collected 33 T cell non-Hodgkin lymphomas (T-NHLs) and analyzed their expression of the BCL-6 protein by immunohistochemistry and investigated the organization of the bcl-6 gene by Southern blot and single strand conformation polymorphism (SSCP). The expression of BCL-6 was demonstrated in 37.5% of lymphoblastic (LBL), 40% of anaplastic large cell (ALCL), and 33% of peripheral T cell lymphomas (PTCL). BCL-6-positive malignant cells exhibited the CD4+ or CD4+/CD8+ phenotype. The bcl-6 gene was in a germline configuration in all T-NHLs examined, and a mutation at the first exon-intron boundary region structure of the wild-type bcl-6 gene was detected in 3 of 12 PTCL. One case of PTCL with mutations of the 5' noncoding region expressed BCL-6. In conclusion, expression of the BCL-6 protein is demonstrable independently of bcl-6 alterations in T-NHLs. This further suggests that molecular mechanisms other than rearrangements and/or mutations of the 5' noncoding region of the bcl-6 gene can result in expression of the protein. Whether these lymphomas arose from T cells expressing BCL-6 or expressed BCL-6 as part of the malignant transformation process needs to be determined. Finally, structural alterations of bcl-6 are rare in T-NHLs, but mutations do occur in the 5' noncoding region. We suggest that expression of BCL-6 in T cells may facilitate lymphomagenesis by repressing critical cytokines and cell cycle regulators.
authors.affiliation: Department of Pathology, the University Hospital of Geneva, Switzerland.
authors.forename: K
authors.initials: K
authors.lastname: Kerl
authors.forename: R
authors.initials: R
authors.lastname: Vonlanthen
authors.forename: M
authors.initials: M
authors.lastname: Nagy
authors.forename: N J
authors.initials: NJ
authors.lastname: Bolzonello
authors.forename: P
authors.initials: P
authors.lastname: Gindre
authors.forename: N
authors.initials: N
authors.lastname: Hurwitz
authors.forename: F
authors.initials: F
authors.lastname: Gudat
authors.forename: R G
authors.initials: RG
authors.lastname: Nador
authors.forename: B
authors.initials: B
authors.lastname: Borisch
mesh_terms: D015139:Blotting, Southern; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry; D016399:Lymphoma, T-Cell / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D009154:Mutation; D010641:Phenotype; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism*; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors