{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T18:09:18Z","timestamp":1789409358152,"version":"build-2803163510"},"reference-count":31,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2005,5,4]],"date-time":"2005-05-04T00:00:00Z","timestamp":1115164800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2005,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Nuclear factor kappa B (NF\u2010\u03baB) activation has been proposed as a cardinal feature of tumourigenesis, although the precise mechanism, frequency, relevance, and extent of NF\u2010\u03baB activation in lymphomas remain to be fully elucidated. In this study, expression profiling and tissue microarray studies of 209 and 323 non\u2010Hodgkin's lymphomas (NHLs) respectively, including the most frequent sub\u2010types of NHL, were employed to generate a hypothesis concerning the most common NF\u2010\u03baB targets in NHL. These analyses showed that NF\u2010\u03baB activation is a common phenomenon in NHL, resulting in the expression of distinct sets of NF\u2010\u03baB target genes, depending on the cell context. <jats:italic>BCL2<\/jats:italic> and <jats:italic>BIRC5<\/jats:italic>\/<jats:italic>Survivin<\/jats:italic> were identified as key NF\u2010\u03baB targets and their expression distinguished small and aggressive B\u2010cell lymphomas, respectively. Interestingly, in the vast majority of B\u2010cell lymphomas, the expression of these markers was mutually exclusive. A set of genes was identified whose expression correlates either with <jats:italic>BIRC5\/Survivin<\/jats:italic> or with <jats:italic>BCL2<\/jats:italic>. <jats:italic>BIRC5\/Survivin<\/jats:italic> expression, in contrast to <jats:italic>BCL2<\/jats:italic>, was associated with a signature of cell proliferation (overexpression of cell cycle control, DNA repair, and polymerase genes), which may contribute to the aggressive phenotype and poor prognosis of these lymphomas. Strikingly, mantle cell lymphoma and chronic lymphocytic leukaemia expressed highly elevated levels of BCL2 protein and mRNA, higher than that observed in reactive mantle zone cells or even in follicular lymphomas, where BCL2 expression is deregulated through the t(14;18) translocation. In parallel with this observation, BIRC5\/Survivin expression was higher in Burkitt's lymphoma and diffuse large B\u2010cell lymphoma than in non\u2010tumoural germinal centre cells. <jats:italic>In vitro<\/jats:italic> studies confirmed that NF\u2010\u03baB activation contributes to the expression of both markers. In cell lines representing aggressive lymphomas, NF\u2010\u03baB inhibition resulted in a decrease in BIRC5\/Survivin expression. Meanwhile, in chronic lymphocytic leukaemia (CLL)\u2010derived lymphocytes, NF\u2010\u03baB inhibition resulted in a marked decrease in BCL2 expression. Copyright \u00a9 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.1768","type":"journal-article","created":{"date-parts":[[2005,5,5]],"date-time":"2005-05-05T00:40:41Z","timestamp":1115253641000},"page":"123-134","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":112,"title":["Expression of the NF\u2010\u03baB targets BCL2 and BIRC5\/Survivin characterizes small B\u2010cell and aggressive B\u2010cell lymphomas, respectively"],"prefix":"10.1002","volume":"206","author":[{"given":"Lorraine","family":"Tracey","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"P\u00e9rez\u2010Rosado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Jes\u00fas","family":"Artiga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisca I","family":"Camacho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"Rodr\u00edguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nerea","family":"Mart\u00ednez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Ruiz\u2010Ballesteros","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Mollejo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Martinez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Cuadros","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan F","family":"Garcia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Lawler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel \u00c1","family":"Piris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,5,4]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-07-2009"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni0302-221"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc780"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(01)00194-7"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1207101"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)00521-X"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/40657"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.3.1526"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1206520"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.194.12.1861"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-11-3574"},{"key":"e_1_2_7_13_2","first-page":"8226","article-title":"The molecular signature of mantle cell lymphoma reveals multiple signals favoring cell survival","volume":"63","author":"Martinez N","year":"2003","journal-title":"Cancer Res"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.1.88"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-0753"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64459-8"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-0269"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1089\/107999004322917034"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-10-3898"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.1661"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0198-69"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110480200"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.28.11.1"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-05-1545"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.34.21096"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M408093200"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-07-2130"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1207336"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)00076-3"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc968"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.7.953"},{"key":"e_1_2_7_32_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20021610"}],"container-title":["The Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpath.1768","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.1768","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T12:55:58Z","timestamp":1761051358000},"score":1,"resource":{"primary":{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/10.1002\/path.1768"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,5,4]]},"references-count":31,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2005,6]]}},"alternative-id":["10.1002\/path.1768"],"URL":"https:\/\/doi.org\/10.1002\/path.1768","archive":["Portico"],"relation":{},"ISSN":["0022-3417","1096-9896"],"issn-type":[{"value":"0022-3417","type":"print"},{"value":"1096-9896","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,5,4]]},"assertion":[{"value":"2005-01-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2005-02-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2005-05-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}