{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:57:34Z","timestamp":1790690254191,"version":"4.1.0"},"reference-count":164,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2019,7,4]],"date-time":"2019-07-04T00:00:00Z","timestamp":1562198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["682435"],"award-info":[{"award-number":["682435"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SCHM220 2.1, CRC1243 project A12 and CRC1335 project P05"],"award-info":[{"award-number":["SCHM220 2.1, CRC1243 project A12 and CRC1335 project P05"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Aberrant constitutive activation of Rel\/NF-\u03baB transcription factors is a hallmark of numerous cancers. Of the five Rel family members, c-Rel has the strongest direct links to tumorigenesis. c-Rel is the only member that can malignantly transform lymphoid cells in vitro. Furthermore, c-Rel is implicated in human B cell lymphoma through the frequent occurrence of REL gene locus gains and amplifications. In normal physiology, high c-Rel expression predominates in the hematopoietic lineage and a diverse range of stimuli can trigger enhanced expression and activation of c-Rel. Both expression and activation of c-Rel are tightly regulated on multiple levels, indicating the necessity to keep its functions under control. In this review we meta-analyze and integrate studies reporting gene locus aberrations to provide an overview on the frequency of REL gains in human B cell lymphoma subtypes, namely follicular lymphoma, diffuse large B cell lymphoma, primary mediastinal B cell lymphoma, and classical Hodgkin lymphoma. We also summarize current knowledge on c-Rel expression and protein localization in these human B cell lymphomas and discuss the co-amplification of BCL11A with REL. In addition, we highlight and illustrate key pathways of c-Rel activation and regulation with a specific focus on B cell biology.<\/jats:p>","DOI":"10.3390\/cancers11070941","type":"journal-article","created":{"date-parts":[[2019,7,4]],"date-time":"2019-07-04T11:13:18Z","timestamp":1562238798000},"page":"941","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["The Unsolved Puzzle of c-Rel in B Cell Lymphoma"],"prefix":"10.3390","volume":"11","author":[{"given":"Maike","family":"Kober-Hasslacher","sequence":"first","affiliation":[{"name":"Institute of Experimental Hematology, School of Medicine, Technical University Munich, Ismaninger Stra\u00dfe 22, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Schmidt-Supprian","sequence":"additional","affiliation":[{"name":"Institute of Experimental Hematology, School of Medicine, Technical University Munich, Ismaninger Stra\u00dfe 22, 81675 Munich, Germany"},{"name":"German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,7,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"a000257","DOI":"10.1101\/cshperspect.a000257","article-title":"Selectivity of the NF-\u03baB Response","volume":"2","author":"Sen","year":"2010","journal-title":"Cold Spring Harb. 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