{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T15:20:16Z","timestamp":1770823216754,"version":"3.50.1"},"reference-count":44,"publisher":"American Society of Hematology","issue":"1","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2001,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>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\u2212, CD8\u2212). 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-XL 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-XLbut not BCL-2. All 4 BCL-6+ T-LBLs and 4 BCL-6\u2212 T-LBLs coexpressed BCL-2 and BCL-XL. 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-XL expression in cortical thymocytes is highly reminiscent of germinal centers, and the abnormal coexpression of BCL-2, BCL-XL, 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.<\/jats:p>","DOI":"10.1182\/blood.v97.1.270","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T08:46:47Z","timestamp":1027759607000},"page":"270-276","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":42,"title":["BCL-6 protein is expressed in precursor T-cell lymphoblastic lymphoma and in prenatal and postnatal thymus"],"prefix":"10.1182","volume":"97","author":[{"given":"Elizabeth","family":"Hyjek","sequence":"first","affiliation":[{"name":"From the Department of Pathology, Weill Medical College of Cornell University, New York, NY."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy","family":"Chadburn","sequence":"additional","affiliation":[{"name":"From the Department of Pathology, Weill Medical College of Cornell University, New York, NY."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi Fang","family":"Liu","sequence":"additional","affiliation":[{"name":"From the Department of Pathology, Weill Medical College of Cornell University, New York, NY."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ethel","family":"Cesarman","sequence":"additional","affiliation":[{"name":"From the Department of Pathology, Weill Medical College of Cornell University, New York, NY."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel M.","family":"Knowles","sequence":"additional","affiliation":[{"name":"From the Department of Pathology, Weill Medical College of Cornell University, New York, 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BCL-6, in diffuse large-cell lymphoma.","volume":"262","author":"Ye","year":"1993","journal-title":"Science."},{"key":"2020021215514785500_B5","doi-asserted-by":"crossref","first-page":"5262","DOI":"10.1073\/pnas.90.11.5262","article-title":"Identification of the gene associated with the recurring chromosomal translocations t(3;14)(q27;q32) and t(3;22)(q27;q11) in B-cell lymphomas.","volume":"90","author":"Baron","year":"1993","journal-title":"Proc Natl Acad Sci U S A."},{"key":"2020021215514785500_B6","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1002\/gcc.2870080303","article-title":"Cloning of a breakpoint cluster region at band 3q27 involved in human non-Hodgkin's lymphoma [see comments].","volume":"8","author":"Deweindt","year":"1993","journal-title":"Genes Chromosomes Cancer."},{"key":"2020021215514785500_B7","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1038\/ng0993-66","article-title":"LAZ3, a novel zinc-finger encoding gene, is disrupted by recurring chromosome 3q27 translocations in human lymphomas.","volume":"5","author":"Kerckaert","year":"1993","journal-title":"Nat Genet."},{"key":"2020021215514785500_B8","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1182\/blood.V83.1.26.bloodjournal83126","article-title":"Gene involved in the 3q27 translocation associated with B-cell lymphoma, BCL5, encodes a Kruppel-like zinc-finger protein.","volume":"83","author":"Miki","year":"1994","journal-title":"Blood."},{"key":"2020021215514785500_B9","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1182\/blood.V83.7.1757.1757","article-title":"Rearrangements of the BCL6 gene in diffuse large cell non-Hodgkin's lymphoma.","volume":"83","author":"Lo Coco","year":"1994","journal-title":"Blood."},{"key":"2020021215514785500_B10","doi-asserted-by":"crossref","first-page":"2423","DOI":"10.1182\/blood.V83.9.2423.2423","article-title":"LAZ3 rearrangements in non-Hodgkin's lymphoma: correlation with histology, immunophenotype, karyotype, and clinical outcome in 217 patients.","volume":"83","author":"Bastard","year":"1994","journal-title":"Blood."},{"key":"2020021215514785500_B11","doi-asserted-by":"crossref","first-page":"2877","DOI":"10.1182\/blood.V85.10.2877.bloodjournal85102877","article-title":"Analysis of LAZ3 (BCL-6) status in B-cell non-Hodgkin's lymphomas: results of rearrangement and gene expression studies and a mutational analysis of coding region sequences.","volume":"85","author":"Otsuki","year":"1995","journal-title":"Blood."},{"key":"2020021215514785500_B12","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1182\/blood.V84.2.397.397","article-title":"Rearrangements of the BCL-6 gene in acquired immunodeficiency syndrome-associated non-Hodgkin's lymphoma: association with diffuse large-cell subtype.","volume":"84","author":"Gaidano","year":"1994","journal-title":"Blood."},{"key":"2020021215514785500_B13","doi-asserted-by":"crossref","first-page":"6209","DOI":"10.1002\/j.1460-2075.1995.tb00311.x","article-title":"Chromosomal translocations cause deregulated BCL6 expression by promoter substitution in B cell lymphoma.","volume":"14","author":"Ye","year":"1995","journal-title":"EMBO J."},{"key":"2020021215514785500_B14","doi-asserted-by":"crossref","first-page":"12520","DOI":"10.1073\/pnas.92.26.12520","article-title":"Frequent somatic hypermutation of the 5\u2032 noncoding region of the BCL6 gene in B-cell lymphoma.","volume":"92","author":"Migliazza","year":"1995","journal-title":"Proc Natl Acad Sci U S A."},{"key":"2020021215514785500_B15","first-page":"3755","article-title":"Frequent mutation of the 5\u2032 noncoding region of the BCL-6 gene in acquired immunodeficiency syndrome-related non-Hodgkin's lymphomas.","volume":"89","author":"Gaidano","year":"1997","journal-title":"Blood."},{"key":"2020021215514785500_B16","doi-asserted-by":"crossref","first-page":"2294","DOI":"10.1182\/blood.V92.7.2294","article-title":"BCL-6 gene mutations in posttransplantation lymphoproliferative disorders predict response to therapy and clinical outcome.","volume":"92","author":"Cesarman","year":"1998","journal-title":"Blood."},{"key":"2020021215514785500_B17","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1182\/blood.V86.1.45.bloodjournal86145","article-title":"BCL-6 protein is expressed in germinal-center B cells.","volume":"86","author":"Cattoretti","year":"1995","journal-title":"Blood."},{"key":"2020021215514785500_B18","doi-asserted-by":"crossref","first-page":"2445","DOI":"10.1182\/blood.V90.6.2445","article-title":"BCL-6 protein expression in human peripheral T-cell neoplasms is restricted to CD30+ anaplastic large-cell lymphomas.","volume":"90","author":"Carbone","year":"1997","journal-title":"Blood."},{"key":"2020021215514785500_B19","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0046-8177(99)90115-6","article-title":"Bcl-6 expression in reactive follicular hyperplasia, follicular lymphoma, and angioimmunoblastic T-cell lymphoma with hyperplastic germinal centers: heterogeneity of intrafollicular T-cells and their altered distribution in the pathogenesis of angioimmunoblastic T-cell lymphoma.","volume":"30","author":"Ree","year":"1999","journal-title":"Hum Pathol."},{"key":"2020021215514785500_B20","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1182\/blood.V86.1.28.bloodjournal86128","article-title":"BCL-6 gene product, a 92- to 98-kD nuclear phosphoprotein, is highly expressed in germinal center B cells and their neoplastic counterparts.","volume":"86","author":"Onizuka","year":"1995","journal-title":"Blood."},{"key":"2020021215514785500_B21","doi-asserted-by":"crossref","first-page":"5257","DOI":"10.1182\/blood.V87.12.5257.bloodjournal87125257","article-title":"BCL-6 expression during B-cell activation.","volume":"87","author":"Allman","year":"1996","journal-title":"Blood."},{"key":"2020021215514785500_B22","first-page":"1543","article-title":"Monoclonal antibodies PG-B6a and PG-B6p recognize, respectively, a highly conserved and a formol-resistant epitope on the human BCL-6 protein amino-terminal region.","volume":"148","author":"Flenghi","year":"1996","journal-title":"Am J Pathol."},{"key":"2020021215514785500_B23","first-page":"405","article-title":"A specific monoclonal antibody (PG-B6) detects expression of the BCL-6 protein in germinal center B cells.","volume":"147","author":"Flenghi","year":"1995","journal-title":"Am J Pathol."},{"key":"2020021215514785500_B24","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1182\/blood.V84.5.1361.1361","article-title":"A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group.","volume":"84","author":"Harris","year":"1994","journal-title":"Blood."},{"key":"2020021215514785500_B25","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1177\/32.2.6198355","article-title":"Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes).","volume":"32","author":"Cordell","year":"1984","journal-title":"J Histochem Cytochem."},{"key":"2020021215514785500_B26","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1093\/nar\/16.3.1215","article-title":"A simple salting out procedure for extracting DNA from human nucleated cells.","volume":"16","author":"Miller","year":"1988","journal-title":"Nucleic Acids Res."},{"key":"2020021215514785500_B27","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1006\/bbrc.1998.8551","article-title":"Expression of the BCL6 gene in the pre- and postnatal mouse.","volume":"247","author":"Bajalica-Lagercrantz","year":"1998","journal-title":"Biochem Biophys Res Commun."},{"key":"2020021215514785500_B28","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1038\/ng0697-161","article-title":"The BCL-6 proto-oncogene controls germinal-centre formation and Th2-type inflammation.","volume":"16","author":"Ye","year":"1997","journal-title":"Nat Genet."},{"key":"2020021215514785500_B29","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1126\/science.276.5312.589","article-title":"Control of inflammation, cytokine expression, and germinal center formation by BCL-6.","volume":"276","author":"Dent","year":"1997","journal-title":"Science."},{"key":"2020021215514785500_B30","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1101\/gad.12.13.1953","article-title":"Antigen receptor signaling induces MAP kinase-mediated phosphorylation and degradation of the BCL-6 transcription factor.","volume":"12","author":"Niu","year":"1998","journal-title":"Genes Dev."},{"key":"2020021215514785500_B31","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1006\/smim.1998.0152","article-title":"Developmental stages in the human thymus.","volume":"11","author":"Res","year":"1999","journal-title":"Semin Immunol."},{"key":"2020021215514785500_B32","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1146\/annurev.immunol.15.1.125","article-title":"Differential signaling by lymphocyte antigen receptors.","volume":"15","author":"Alberola-Ila","year":"1997","journal-title":"Annu Rev Immunol."},{"key":"2020021215514785500_B33","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1146\/annurev.immunol.14.1.73","article-title":"Cellular interactions in thymocyte development.","volume":"14","author":"Anderson","year":"1996","journal-title":"Annu Rev Immunol."},{"key":"2020021215514785500_B34","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1038\/373620a0","article-title":"Selective requirement for MAP kinase activation in thymocyte differentiation.","volume":"373","author":"Alberola-Ila","year":"1995","journal-title":"Nature."},{"key":"2020021215514785500_B35","doi-asserted-by":"crossref","first-page":"2350","DOI":"10.1002\/eji.1830261012","article-title":"Raf regulates positive selection.","volume":"26","author":"O'Shea","year":"1996","journal-title":"Eur J Immunol."},{"key":"2020021215514785500_B36","doi-asserted-by":"crossref","first-page":"6961","DOI":"10.1073\/pnas.88.16.6961","article-title":"BCL2 protein is topographically restricted in tissues characterized by apoptotic cell death.","volume":"88","author":"Hockenbery","year":"1991","journal-title":"Proc Natl Acad Sci U S A."},{"key":"2020021215514785500_B37","doi-asserted-by":"crossref","first-page":"1973","DOI":"10.1084\/jem.182.6.1973","article-title":"Bcl-XL displays restricted distribution during T cell development and inhibits multiple forms of apoptosis but not clonal deletion in transgenic mice.","volume":"182","author":"Grillot","year":"1995","journal-title":"J Exp Med."},{"key":"2020021215514785500_B38","doi-asserted-by":"crossref","first-page":"4763","DOI":"10.1073\/pnas.92.11.4763","article-title":"Bclx regulates the survival of double-positive thymocytes.","volume":"92","author":"Ma","year":"1995","journal-title":"Proc Natl Acad Sci U S A."},{"key":"2020021215514785500_B39","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1146\/annurev.immunol.16.1.395","article-title":"BCL-2 family: regulators of cell death.","volume":"16","author":"Chao","year":"1998","journal-title":"Annu Rev Immunol."},{"key":"2020021215514785500_B40","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/1074-7613(94)90098-1","article-title":"Bcl-2 is upregulated at the CD4+ CD8+ stage during positive selection and promotes thymocyte differentiation at several control points.","volume":"1","author":"Linette","year":"1994","journal-title":"Immunity."},{"key":"2020021215514785500_B41","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1084\/jem.179.1.145","article-title":"The T cell receptor repertoire of CD4\u20138+ thymocytes is altered by overexpression of the BCL-2 protooncogene in the thymus.","volume":"179","author":"Tao","year":"1994","journal-title":"J Exp Med."},{"key":"2020021215514785500_B42","first-page":"743","article-title":"Abnormal thymocyte development and generation of autoreactive T cells in mixed and cortical thymomas.","volume":"78","author":"Nenninger","year":"1998","journal-title":"Lab Invest."},{"key":"2020021215514785500_B43","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/S0046-8177(99)90141-7","article-title":"Bcl-6 and Bcl-2 protein expression in diffuse large B-cell lymphoma and follicular lymphoma: correlation with 3q27 and 18q21 chromosomal abnormalities.","volume":"30","author":"Skinnider","year":"1999","journal-title":"Hum Pathol."},{"key":"2020021215514785500_B44","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1182\/blood.V91.1.244","article-title":"Unbalanced expression of bcl-2 family proteins in follicular lymphoma: contribution of CD40 signaling in promoting survival.","volume":"91","author":"Ghia","year":"1998","journal-title":"Blood."}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/ashpublications.org\/blood\/article-pdf\/97\/1\/270\/1670331\/270.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/ashpublications.org\/blood\/article-pdf\/97\/1\/270\/1670331\/270.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,2,12]],"date-time":"2020-02-12T15:52:07Z","timestamp":1581522727000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/97\/1\/270\/52902\/BCL6-protein-is-expressed-in-precursor-Tcell"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,1,1]]},"references-count":44,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2001,1,1]]}},"URL":"https:\/\/doi.org\/10.1182\/blood.v97.1.270","relation":{},"ISSN":["1528-0020","0006-4971"],"issn-type":[{"value":"1528-0020","type":"electronic"},{"value":"0006-4971","type":"print"}],"subject":[],"published":{"date-parts":[[2001,1,1]]}}}