{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T14:40:52Z","timestamp":1790260852808,"version":"4.1.0"},"reference-count":32,"publisher":"American Society of Hematology","issue":"12","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2001,6,15]]},"abstract":"<jats:p>Polycomb-group (PcG) proteins, such as BMI-1 and EZH2, form multimeric gene-repressing complexes involved in axial patterning, hematopoiesis, and cell cycle regulation. In addition, BMI-1 is involved in experimental lymphomagenesis. Little is known about its role in human lymphomagenesis. Here, BMI-1 and EZH2 expression patterns are analyzed in a variety of B-cell non-Hodgkin lymphomas (B-NHLs), including small lymphocytic lymphoma, follicular lymphoma, large B-cell lymphoma, mantle-cell lymphoma, and Burkitt lymphoma. In contrast to the mutually exclusive pattern of BMI-1 and EZH2 in reactive follicles, the neoplastic cells in B-NHLs of intermediate- and high-grade malignancy showed strong coexpression of BMI-1 and EZH2. This pattern overlapped with the expression of Mib-1\/Ki-67, a marker for proliferation. Neoplastic cells in B-NHL of low-grade malignancy were either BMI-1low\/EZH2+ (neoplastic centroblasts) or BMI-1lowEZH2\u2212(neoplastic centrocytes). These observations show that low-, intermediate-, and high grade B-NHLs are associated with increased coexpression of the BMI-1 and EZH2 PcG proteins, whose normal expression pattern is mutually exclusive. This expression pattern is probably caused by a failure to down-regulate BMI-1 in dividing neoplastic cells, because BMI-1 expression is absent from normal dividing B cells. These observations are in agreement with findings in studies of Bmi-1 transgenic mice. The extent of BMI-1\/EZH2 coexpression correlated with clinical grade and the presence of Mib-1\/Ki-67 expression, suggesting that the irregular expression of BMI-1 and EZH2 is an early event in the formation of B-NHL. This points to a role for abnormal PcG expression in human lymphomagenesis.<\/jats:p>","DOI":"10.1182\/blood.v97.12.3896","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T12:46:40Z","timestamp":1027774000000},"page":"3896-3901","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":223,"title":["Coexpression of BMI-1 and EZH2 polycomb-group proteins is associated with cycling cells and degree of malignancy in B-cell non-Hodgkin lymphoma"],"prefix":"10.1182","volume":"97","author":[{"given":"Folkert J.","family":"van Kemenade","sequence":"first","affiliation":[{"name":"From the Department of Pathology, VU University Hospital, Amsterdam; and Swammerdam Institute for Life Sciences, BioCentrum Amsterdam, University of Amsterdam, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank M.","family":"Raaphorst","sequence":"additional","affiliation":[{"name":"From the Department of Pathology, VU University Hospital, Amsterdam; and Swammerdam Institute for Life Sciences, BioCentrum Amsterdam, University of Amsterdam, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tjasso","family":"Blokzijl","sequence":"additional","affiliation":[{"name":"From the Department of Pathology, VU University Hospital, Amsterdam; and Swammerdam Institute for Life Sciences, BioCentrum Amsterdam, University of Amsterdam, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elly","family":"Fieret","sequence":"additional","affiliation":[{"name":"From the Department of Pathology, VU University Hospital, Amsterdam; and Swammerdam Institute for Life Sciences, BioCentrum Amsterdam, University of Amsterdam, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karien M.","family":"Hamer","sequence":"additional","affiliation":[{"name":"From the Department of Pathology, VU University Hospital, Amsterdam; and Swammerdam Institute for Life Sciences, BioCentrum Amsterdam, University of Amsterdam, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David P. E.","family":"Satijn","sequence":"additional","affiliation":[{"name":"From the Department of Pathology, VU University Hospital, Amsterdam; and Swammerdam Institute for Life Sciences, BioCentrum Amsterdam, University of Amsterdam, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arie P.","family":"Otte","sequence":"additional","affiliation":[{"name":"From the Department of Pathology, VU University Hospital, Amsterdam; and Swammerdam Institute for Life Sciences, BioCentrum Amsterdam, University of Amsterdam, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris J. L. 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