{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T12:19:37Z","timestamp":1791116377263,"version":"4.1.0"},"reference-count":32,"publisher":"National Academy of Sciences","issue":"12","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2003,6,10]]},"abstract":"<jats:p>Follicular lymphoma (FL) is the most common form of low-grade non-Hodgkin's  lymphoma. Transformation to diffuse large B cell lymphoma (DLBCL) is an  important cause of mortality. Using cDNA microarray analysis we identified 113  transformation-associated genes whose expression differed consistently between  serial clonally related samples of FL and DLBCL occurring within the same  individual. Quantitative RT-PCR validated the microarray results and assigned  blinded independent group of 20 FLs, 20 DLBCLs, and five transformed  lymphoma-derived cell lines with 100%, 70%, and 100% accuracy, respectively.  Notably, growth factor cytokine receptors and p38\u03b2-mitogen-activated  protein kinase (MAPK) were differentially expressed in the DLBCLs.  Immunohistochemistry of another blinded set of samples demonstrated expression  of phosphorylated p38MAPK in 6\/6 DLBCLs and 1\/5 FLs, but not in benign  germinal centers. SB203580 an inhibitor of p38MAPK specifically induced  caspase-3-mediated apoptosis in t(14;18)+\/p38MAPK+-transformed FL-derived cell  lines. Lymphoma growth was also inhibited in SB203580-treated NOD-SCID mice.  Our results implicate p38MAPK dysregulation in FL transformation and suggest  that molecular targeting of specific elements within this pathway should be  explored for transformed FL therapy.<\/jats:p>","DOI":"10.1073\/pnas.1137463100","type":"journal-article","created":{"date-parts":[[2003,6,10]],"date-time":"2003-06-10T13:06:36Z","timestamp":1055250396000},"page":"7259-7264","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":141,"title":["Involvement of multiple signaling pathways in follicular lymphoma  transformation: p38-mitogen-activated protein kinase as a target for  therapy"],"prefix":"10.1073","volume":"100","author":[{"given":"Kojo S. J.","family":"Elenitoba-Johnson","sequence":"first","affiliation":[{"name":"Department of Pathology,  Associated Regional and University  Pathologists Institute for Clinical and Experimental Pathology,  Department of Mathematics, and  Division of Medical Oncology, University of  Utah, Salt Lake City, UT 84132; Cross Cancer  Institute, Edmonton, AB, Canada T6G 1Z2; and  Advanced Therapeutics Program and  Department of Pathology, Sunnybrook  and Women's College Health Sciences Centre, Toronto, ON, Canada M4N 3M5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen D.","family":"Jenson","sequence":"additional","affiliation":[{"name":"Department of Pathology,  Associated Regional and University  Pathologists Institute for Clinical and Experimental Pathology,  Department of Mathematics, and  Division of Medical Oncology, University of  Utah, Salt Lake City, UT 84132; Cross Cancer  Institute, Edmonton, AB, Canada T6G 1Z2; and  Advanced Therapeutics Program and  Department of Pathology, Sunnybrook  and Women's College Health Sciences Centre, Toronto, ON, Canada M4N 3M5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert T.","family":"Abbott","sequence":"additional","affiliation":[{"name":"Department of Pathology,  Associated Regional and University  Pathologists Institute for Clinical and Experimental Pathology,  Department of Mathematics, and  Division of Medical Oncology, University of  Utah, Salt Lake City, UT 84132; Cross Cancer  Institute, Edmonton, AB, Canada T6G 1Z2; and  Advanced Therapeutics Program and  Department of Pathology, Sunnybrook  and Women's College Health Sciences Centre, Toronto, ON, Canada M4N 3M5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Palais","sequence":"additional","affiliation":[{"name":"Department of Pathology,  Associated Regional and University  Pathologists Institute for Clinical and Experimental Pathology,  Department of Mathematics, and  Division of Medical Oncology, University of  Utah, Salt Lake City, UT 84132; Cross Cancer  Institute, Edmonton, AB, Canada T6G 1Z2; and  Advanced Therapeutics Program and  Department of Pathology, Sunnybrook  and Women's College Health Sciences Centre, Toronto, ON, Canada M4N 3M5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra D.","family":"Bohling","sequence":"additional","affiliation":[{"name":"Department of Pathology,  Associated Regional and University  Pathologists Institute for Clinical and Experimental Pathology,  Department of Mathematics, and  Division of Medical Oncology, University of  Utah, Salt Lake City, UT 84132; Cross Cancer  Institute, Edmonton, AB, Canada T6G 1Z2; and  Advanced Therapeutics Program and  Department of Pathology, Sunnybrook  and Women's College Health Sciences Centre, Toronto, ON, Canada M4N 3M5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaosheng","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pathology,  Associated Regional and University  Pathologists Institute for Clinical and Experimental Pathology,  Department of Mathematics, and  Division of Medical Oncology, University of  Utah, Salt Lake City, UT 84132; Cross Cancer  Institute, Edmonton, AB, Canada T6G 1Z2; and  Advanced Therapeutics Program and  Department of Pathology, Sunnybrook  and Women's College Health Sciences Centre, Toronto, ON, Canada M4N 3M5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheryl","family":"Tripp","sequence":"additional","affiliation":[{"name":"Department of Pathology,  Associated Regional and University  Pathologists Institute for Clinical and Experimental Pathology,  Department of Mathematics, and  Division of Medical Oncology, University of  Utah, Salt Lake City, UT 84132; Cross Cancer  Institute, Edmonton, AB, Canada T6G 1Z2; and  Advanced Therapeutics Program and  Department of Pathology, Sunnybrook  and Women's College Health Sciences Centre, Toronto, ON, Canada M4N 3M5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Shami","sequence":"additional","affiliation":[{"name":"Department of Pathology,  Associated Regional and University  Pathologists Institute for Clinical and Experimental Pathology,  Department of Mathematics, and  Division of Medical Oncology, University of  Utah, Salt Lake City, UT 84132; Cross Cancer  Institute, Edmonton, AB, Canada T6G 1Z2; and  Advanced Therapeutics Program and  Department of Pathology, Sunnybrook  and Women's College Health Sciences Centre, Toronto, ON, Canada M4N 3M5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lai Y.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology,  Associated Regional and University  Pathologists Institute for Clinical and Experimental Pathology,  Department of Mathematics, and  Division of Medical Oncology, University of  Utah, Salt Lake City, UT 84132; Cross Cancer  Institute, Edmonton, AB, Canada T6G 1Z2; and  Advanced Therapeutics Program and  Department of Pathology, Sunnybrook  and Women's College Health Sciences Centre, Toronto, ON, Canada M4N 3M5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert W.","family":"Coupland","sequence":"additional","affiliation":[{"name":"Department of Pathology,  Associated Regional and University  Pathologists Institute for Clinical and Experimental Pathology,  Department of Mathematics, and  Division of Medical Oncology, University of  Utah, Salt Lake City, UT 84132; Cross Cancer  Institute, Edmonton, AB, Canada T6G 1Z2; and  Advanced Therapeutics Program and  Department of Pathology, Sunnybrook  and Women's College Health Sciences Centre, Toronto, ON, Canada M4N 3M5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rena","family":"Buckstein","sequence":"additional","affiliation":[{"name":"Department of Pathology,  Associated Regional and University  Pathologists Institute for Clinical and Experimental Pathology,  Department of Mathematics, and  Division of Medical Oncology, University of  Utah, Salt Lake City, UT 84132; Cross Cancer  Institute, Edmonton, AB, Canada T6G 1Z2; and  Advanced Therapeutics Program and  Department of Pathology, Sunnybrook  and Women's College Health Sciences Centre, Toronto, ON, Canada M4N 3M5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bayardo","family":"Perez-Ordonez","sequence":"additional","affiliation":[{"name":"Department of Pathology,  Associated Regional and University  Pathologists Institute for Clinical and Experimental Pathology,  Department of Mathematics, and  Division of Medical Oncology, University of  Utah, Salt Lake City, UT 84132; Cross Cancer  Institute, Edmonton, AB, Canada T6G 1Z2; and  Advanced Therapeutics Program and  Department of Pathology, Sunnybrook  and Women's College Health Sciences Centre, Toronto, ON, Canada M4N 3M5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherrie L.","family":"Perkins","sequence":"additional","affiliation":[{"name":"Department of Pathology,  Associated Regional and University  Pathologists Institute for Clinical and Experimental Pathology,  Department of Mathematics, and  Division of Medical Oncology, University of  Utah, Salt Lake City, UT 84132; Cross Cancer  Institute, Edmonton, AB, Canada T6G 1Z2; and  Advanced Therapeutics Program and  Department of Pathology, Sunnybrook  and Women's College Health Sciences Centre, Toronto, ON, Canada M4N 3M5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian D.","family":"Dube","sequence":"additional","affiliation":[{"name":"Department of Pathology,  Associated Regional and University  Pathologists Institute for Clinical and Experimental Pathology,  Department of Mathematics, and  Division of Medical Oncology, University of  Utah, Salt Lake City, UT 84132; Cross Cancer  Institute, Edmonton, AB, Canada T6G 1Z2; and  Advanced Therapeutics Program and  Department of Pathology, Sunnybrook  and Women's College Health Sciences Centre, Toronto, ON, Canada M4N 3M5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan S.","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Pathology,  Associated Regional and University  Pathologists Institute for Clinical and Experimental Pathology,  Department of Mathematics, and  Division of Medical Oncology, University of  Utah, Salt Lake City, UT 84132; Cross Cancer  Institute, Edmonton, AB, Canada T6G 1Z2; and  Advanced Therapeutics Program and  Department of Pathology, Sunnybrook  and Women's College Health Sciences Centre, Toronto, ON, Canada M4N 3M5"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2003,5,19]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1998.16.8.2780"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198412063112303"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1988.6.5.919"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.6093263"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/348334a0"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(89)90174-8"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V82.7.1994.1994"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V82.8.2289.2289"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V91.12.4677"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V91.8.2977.2977_2977_2984"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2264(199805)22:1<72::AID-GCC10>3.0.CO;2-K"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V80.3.758.758"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.2.635.014k37_635_639"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.132253599"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/35000501"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5439.531"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.141.9.7666"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3780169"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/74546"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.270.5235.467"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.25.14863"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)61742-7"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(95)00072-I"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.121.1.145"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.98.1.247"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V95.3.992.003k29_992_998"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M001281200"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0797-260"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.10.6783"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205150"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109764200"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/elps.1150150165"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1137463100","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,25]],"date-time":"2022-04-25T21:25:57Z","timestamp":1650921957000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1137463100"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,5,19]]},"references-count":32,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2003,6,10]]}},"alternative-id":["10.1073\/pnas.1137463100"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1137463100","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,5,19]]},"assertion":[{"value":"2002-12-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2003-04-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2003-05-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}