title: BCL-6 protein is expressed in precursor T-cell lymphoblastic lymphoma and in prenatal and postnatal thymus.
abstract: The organization and expression of the BCL-6 gene in normal and neoplastic thymic T cells has not been fully determined. We examined 8 precursor T-cell lymphoblastic lymphomas (T-LBLs) and found significant BCL-6 expression in 4 cases. Three of the BCL-6(+) cases expressed a common thymocyte phenotype (CD4(+), CD8(+)), and one expressed a precursor thymocyte phenotype (CD4(-), CD8(-)). In 6 cases evaluated, including those expressing BCL-6, molecular analyses demonstrated a germline configuration of the BCL-6 gene and a wild-type BCL-6 gene first exon-intron boundary region. We also evaluated 12 normal prenatal and postnatal thymuses for BCL-6 protein. BCL-6 was expressed by most cortical thymocytes and by scattered medullary thymocytes. BCL-6(+) cortical and medullary thymocytes also expressed CD2, CD3, CD4, CD5, CD7, or CD8. We further analyzed the pattern of BCL-2 and BCL-X(L) expression and their coexpression with BCL-6 in normal thymus and T-LBL and compared it to that of follicle centers of reactive lymph nodes and follicular lymphoma. BCL-6(+) cortical thymocytes coexpressed BCL-X(L) but not BCL-2. All 4 BCL-6(+) T-LBLs and 4 BCL-6(-) T-LBLs coexpressed BCL-2 and BCL-X(L). Conceivably, T-LBLs may arise through clonal expansion of cortical thymocytes normally expressing the BCL-6 protein. The pattern of BCL-6, BCL-2, and BCL-X(L) expression in cortical thymocytes is highly reminiscent of germinal centers, and the abnormal coexpression of BCL-2, BCL-X(L), and BCL-6 in T-LBL is analogous to coexpression in follicle center cell lymphomas, suggesting that coexpression of these anti-apoptotic genes may contribute to the pathogenesis of T-LBL.
authors.affiliation: Department of Pathology, Weill Medical College of Cornell University, New York, NY 10021, USA.
authors.forename: E
authors.initials: E
authors.lastname: Hyjek
authors.forename: A
authors.initials: A
authors.lastname: Chadburn
authors.forename: Y F
authors.initials: YF
authors.lastname: Liu
authors.forename: E
authors.initials: E
authors.lastname: Cesarman
authors.forename: D M
authors.initials: DM
authors.lastname: Knowles
mesh_terms: D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000737:chemistry / Q000166:cytology; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D007231:Infant, Newborn; D008224:Lymphoma, Follicular / Q000209:etiology / Q000378:metabolism; D016399:Lymphoma, T-Cell / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051560:Proto-Oncogene Proteins c-bcl-6; D013950:Thymus Gland / Q000737:chemistry / Q000196:embryology* / Q000473:pathology; D014157:Transcription Factors / Q000378:metabolism*; D051020:bcl-X Protein
chemical_list: C494811:BCL2L1 protein, human; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors; D051020:bcl-X Protein