{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T09:03:50Z","timestamp":1789376630600,"version":"build-2803163510"},"reference-count":72,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,7,9]],"date-time":"2013-07-09T00:00:00Z","timestamp":1373328000000},"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":[[2013,8]]},"abstract":"Abstract<\/jats:title>Hodgkin's lymphoma is unusual among B cell lymphomas, in so far as the malignant Hodgkin\/Reed\u2013Sternberg (HRS<\/jats:styled-content>) cells lack a functional B cell receptor (BCR<\/jats:styled-content>), as well as many of the required downstream signalling components. In Epstein\u2013Barr virus (EBV<\/jats:styled-content>)\u2010positive cases of Hodgkin's lymphoma, HRS<\/jats:styled-content> cells express the viral latent membrane proteins (LMP<\/jats:styled-content>)\u20101 and \u20102A<\/jats:styled-content>. LMP2A<\/jats:styled-content> is thought to contribute to the pathogenesis of Hodgkin's lymphoma by providing a surrogate BCR<\/jats:styled-content>\u2010like survival signal. However, LMP2A<\/jats:styled-content> has also been shown to induce the virus\u2010replicative cycle in B cells, an event presumably incompatible with lymphomagenesis. In an attempt to resolve this apparent paradox, we compared the transcriptional changes observed in primary HRS<\/jats:styled-content> cells with those induced by LMP2A<\/jats:styled-content> and by BCR<\/jats:styled-content> activation in primary human germinal centre (GC<\/jats:styled-content>) B cells, the presumed progenitors of HRS<\/jats:styled-content> cells. We found a subset of genes that were up\u2010regulated by both LMP2A<\/jats:styled-content> expression and BCR<\/jats:styled-content> activation but which were down\u2010regulated in primary HRS<\/jats:styled-content> cells. These genes included EGR1<\/jats:styled-content><\/jats:italic>, an immediate\u2010early gene that is required for BCR<\/jats:styled-content>\u2010induced entry to the virus\u2010replicative cycle. We present data supporting a model for the pathogenesis of EBV<\/jats:styled-content>\u2010positive Hodgkin's lymphoma in which LMP2A<\/jats:styled-content>\u2010expressing HRS<\/jats:styled-content> cells lacking BCR<\/jats:styled-content> signalling functions cannot induce EGR1<\/jats:styled-content><\/jats:italic> and are consequently protected from entry to the virus lytic cycle. The primary microarray data are available from GEO<\/jats:styled-content> (<\/jats:bold>http:\/\/www.ncbi.nlm.nih.gov\/geo\/<\/jats:ext-link>) under series Accession No 46143. Copyright \u00a9 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.<\/jats:bold><\/jats:p>","DOI":"10.1002\/path.4198","type":"journal-article","created":{"date-parts":[[2013,4,16]],"date-time":"2013-04-16T14:10:41Z","timestamp":1366121441000},"page":"399-409","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Suppression of the LMP2A<\/scp> target gene, EGR<\/scp>\u20101<\/i>, protects Hodgkin's lymphoma cells from entry to the EBV<\/scp> lytic cycle"],"prefix":"10.1002","volume":"230","author":[{"given":"Martina","family":"Vockerodt","sequence":"first","affiliation":[{"name":"School of Cancer Sciences University of Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbin","family":"Wei","sequence":"additional","affiliation":[{"name":"School of Cancer Sciences University of Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eszter","family":"Nagy","sequence":"additional","affiliation":[{"name":"School of Cancer Sciences University of Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuzana","family":"Prouzova","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pathology, Department of Pathology, and Institute of Molecular and Translation Medicine, Faculty of Medicine and Dentistry Palacky University Olomouc Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Schrader","sequence":"additional","affiliation":[{"name":"Department of Haematology and Oncology University Medical Centre of the Georg\u2010August University of G\u00f6ttingen; GRK 1034 of the Deutsche Forschungsgemeinschaft at the University Medical Centre G\u00f6ttingen; and Network Molecular Mechanism of Malignant Lymphoma (MMML) of the Deutsche Krebshilfe Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dieter","family":"Kube","sequence":"additional","affiliation":[{"name":"Department of Haematology and Oncology University Medical Centre of the Georg\u2010August University of G\u00f6ttingen; GRK 1034 of the Deutsche Forschungsgemeinschaft at the University Medical Centre G\u00f6ttingen; and Network Molecular Mechanism of Malignant Lymphoma (MMML) of the Deutsche Krebshilfe Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Rowe","sequence":"additional","affiliation":[{"name":"School of Cancer Sciences University of Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciaran B","family":"Woodman","sequence":"additional","affiliation":[{"name":"School of Cancer Sciences University of Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul G","family":"Murray","sequence":"additional","affiliation":[{"name":"School of Cancer Sciences University of Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,7,9]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"2655","volume-title":"Fields' Virology","author":"Rickinson A","year":"2007"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1206556"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200323765"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1589"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.21716"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-06-2342"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-06-2341"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-06-2327"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5438.300"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80623-8"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1036"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.1.105-114.2003"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-05-090142"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20080238"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-10-117655"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.2384"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-09-307710"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-04-1018"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1808"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.194.3.255"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V97.2.496"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-03-0839"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.9.5.2083"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.181.1.417"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1997.8690"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01415-10"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.69.6.3816-3823.1995"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02608-05"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.007922-0"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-02-338434"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.2.772"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.80440-0"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/1478-811X-10-9"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V78.5.1162.1162"},{"key":"e_1_2_7_36_1","first-page":"1315","article-title":"A survey of Epstein\u2013Barr virus gene expression in sporadic non\u2010Hodgkin's lymphomas. 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