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We performed a genome-wide expression study of microdissected L&amp;H lymphoma cells in comparison to normal and other malignant B cells that indicated a relationship of L&amp;H cells to and\/or that they originate from germinal center B cells at the transition to memory B cells. L&amp;H cells show a surprisingly high similarity to the tumor cells of T cell\u2013rich B cell lymphoma and classical Hodgkin lymphoma, a partial loss of their B cell phenotype, and deregulation of many apoptosis regulators and putative oncogenes. Importantly, L&amp;H cells are characterized by constitutive nuclear factor \u03baB activity and aberrant extracellular signal-regulated kinase signaling. Thus, these findings shed new light on the nature of L&amp;H cells, reveal several novel pathogenetic mechanisms in NLPHL, and may help in differential diagnosis and lead to novel therapeutic strategies.<\/jats:p>","DOI":"10.1084\/jem.20080809","type":"journal-article","created":{"date-parts":[[2008,9,15]],"date-time":"2008-09-15T21:09:38Z","timestamp":1221512978000},"page":"2251-2268","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":320,"title":["Origin and pathogenesis of nodular lymphocyte\u2013predominant Hodgkin lymphoma as revealed by global gene expression analysis"],"prefix":"10.1084","volume":"205","author":[{"given":"Verena","family":"Brune","sequence":"first","affiliation":[{"name":"1Institute for Cell Biology (Tumor Research), University of Duisburg-Essen Medical School, 45122 Essen, Germany"},{"name":"2Institute for Pathology, University of Frankfurt Medical School, 60590 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Tiacci","sequence":"additional","affiliation":[{"name":"1Institute for Cell Biology (Tumor Research), University of Duisburg-Essen Medical School, 45122 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ines","family":"Pfeil","sequence":"additional","affiliation":[{"name":"1Institute for Cell Biology (Tumor Research), University of Duisburg-Essen Medical School, 45122 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Do\u0308ring","sequence":"additional","affiliation":[{"name":"2Institute for Pathology, University of Frankfurt Medical School, 60590 Frankfurt, Germany"},{"name":"7Institute for Informatics, University of Frankfurt, 60054 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Eckerle","sequence":"additional","affiliation":[{"name":"2Institute for Pathology, University of Frankfurt Medical School, 60590 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carel J.M.","family":"van Noesel","sequence":"additional","affiliation":[{"name":"3Department of Pathology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfram","family":"Klapper","sequence":"additional","affiliation":[{"name":"4Institute for Pathology, University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brunangelo","family":"Falini","sequence":"additional","affiliation":[{"name":"5Institute of Hematology, University of Perugia, 06100 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"von Heydebreck","sequence":"additional","affiliation":[{"name":"6Bio- and Chemoinformatics, Merck KGaA, 64293 Darmstadt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Metzler","sequence":"additional","affiliation":[{"name":"7Institute for Informatics, University of Frankfurt, 60054 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Bra\u0308uninger","sequence":"additional","affiliation":[{"name":"2Institute for Pathology, University of Frankfurt Medical School, 60590 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin-Leo","family":"Hansmann","sequence":"additional","affiliation":[{"name":"2Institute for Pathology, University of Frankfurt Medical School, 60590 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Ku\u0308ppers","sequence":"additional","affiliation":[{"name":"1Institute for Cell Biology (Tumor Research), University of Duisburg-Essen Medical School, 45122 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2008,9,15]]},"reference":[{"key":"2023072516264800600_BIB1","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/S0065-230X(02)84009-X","volume":"84","year":"2002","journal-title":"Adv. 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