{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T02:28:38Z","timestamp":1791167318335,"version":"4.1.0"},"reference-count":24,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,10,28]],"date-time":"2013-10-28T00:00:00Z","timestamp":1382918400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2014,1]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    Cereblon, a member of the cullin 4 ring ligase complex (\n                    <jats:styled-content style=\"fixed-case\">CRL<\/jats:styled-content>\n                    4), is the molecular target of the immunomodulatory drugs (\n                    <jats:styled-content style=\"fixed-case\">IM<\/jats:styled-content>\n                    i\n                    <jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>\n                    s) lenalidomide and pomalidomide and is required for the antiproliferative activity of these agents in multiple myeloma (\n                    <jats:styled-content style=\"fixed-case\">MM<\/jats:styled-content>\n                    ) and immunomodulatory activity in\n                    <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>\n                    cells. Cereblon's central role as a target of lenalidomide and pomalidomide suggests potential utility as a predictive biomarker of response or resistance to\n                    <jats:styled-content style=\"fixed-case\">IM<\/jats:styled-content>\n                    i\n                    <jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>\n                    therapy. Our studies characterized a cereblon monoclonal antibody\n                    <jats:styled-content style=\"fixed-case\">CRBN<\/jats:styled-content>\n                    65, with high sensitivity and specificity in\n                    <jats:styled-content style=\"fixed-case\">W<\/jats:styled-content>\n                    estern analysis and immunohistochemistry that is superior to commercially available antibodies. We identified multiple cereblon splice variants in both\n                    <jats:styled-content style=\"fixed-case\">MM<\/jats:styled-content>\n                    cell lines and primary cells, highlighting challenges with conventional gene expression assays given this gene complexity. Using\n                    <jats:styled-content style=\"fixed-case\">CRBN<\/jats:styled-content>\n                    65 antibody and\n                    <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>\n                    aq\n                    <jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>\n                    an quantitative reverse transcription polymerase chain reaction assays, we showed lack of correlation between cereblon protein and\n                    <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>\n                    levels. Furthermore, lack of correlation between cereblon expression in\n                    <jats:styled-content style=\"fixed-case\">MM<\/jats:styled-content>\n                    cell lines and sensitivity to lenalidomide was shown. In cell lines made resistant to lenalidomide and pomalidomide, cereblon protein is greatly reduced. These studies show limitations to the current approaches of cereblon measurement that rely on commercial reagents and assays. Standardized reagents and validated assays are needed to accurately assess the role of cereblon as a predictive biomarker.\n                  <\/jats:p>","DOI":"10.1111\/bjh.12622","type":"journal-article","created":{"date-parts":[[2013,10,28]],"date-time":"2013-10-28T04:59:56Z","timestamp":1382936396000},"page":"233-244","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":90,"title":["Measuring cereblon as a biomarker of response or resistance to lenalidomide and pomalidomide requires use of standardized reagents and understanding of gene complexity"],"prefix":"10.1111","volume":"164","author":[{"given":"Anita K.","family":"Gandhi","sequence":"first","affiliation":[{"name":"Celgene Corporation Summit NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek","family":"Mendy","sequence":"additional","affiliation":[{"name":"Celgene Corporation San Diego USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Waldman","sequence":"additional","affiliation":[{"name":"Celgene Corporation Summit NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gengxin","family":"Chen","sequence":"additional","affiliation":[{"name":"Celgene Corporation San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Rychak","sequence":"additional","affiliation":[{"name":"Celgene Corporation San Diego USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Miller","sequence":"additional","affiliation":[{"name":"Celgene Corporation San Diego USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana","family":"Gaidarova","sequence":"additional","affiliation":[{"name":"Celgene Corporation San Diego USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Ren","sequence":"additional","affiliation":[{"name":"Celgene Corporation San Diego USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Wang","sequence":"additional","affiliation":[{"name":"Celgene Corporation San Diego USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Breider","sequence":"additional","affiliation":[{"name":"Celgene Corporation San Diego USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Carmel","sequence":"additional","affiliation":[{"name":"Celgene Corporation San Diego USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afshin","family":"Mahmoudi","sequence":"additional","affiliation":[{"name":"Celgene Corporation San Diego USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilgrim","family":"Jackson","sequence":"additional","affiliation":[{"name":"Celgene Corporation San Diego USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahan","family":"Abbasian","sequence":"additional","affiliation":[{"name":"Celgene Corporation San Diego USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian E.","family":"Cathers","sequence":"additional","affiliation":[{"name":"Celgene Corporation San Diego USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter H.","family":"Schafer","sequence":"additional","affiliation":[{"name":"Celgene Corporation Summit NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom O.","family":"Daniel","sequence":"additional","affiliation":[{"name":"Celgene Corporation Summit NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"Lopez\u2010Girona","sequence":"additional","affiliation":[{"name":"Celgene Corporation San Diego USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjan","family":"Thakurta","sequence":"additional","affiliation":[{"name":"Celgene Corporation Summit NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajesh","family":"Chopra","sequence":"additional","affiliation":[{"name":"Celgene Corporation Summit NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,10,28]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0030159"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-06-438101"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09837"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkr991"},{"key":"e_1_2_8_6_1","first-page":"S182","article-title":"Exon mutations in cereblon (CRBN) and DNA damage binding protein 1 (DDB1) genes are rare in myeloma cells and patients","volume":"13","author":"Gandhi A.K.","year":"2013","journal-title":"Clinical Lymphoma Myeloma and Leukemia"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)00316-7"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.12338"},{"key":"e_1_2_8_9_1","unstructured":"International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. (1995)Guidelines for industry: text on validation of analytical procedures.http:\/\/www.labcompliance.de\/documents\/international\/ich\/h-307-ich-fda-methods-terminology-ichq2a.pdf. Accessed September 9 2013."},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1177319"},{"key":"e_1_2_8_11_1","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1182\/blood.V120.21.931.931","article-title":"High cereblon protein expression correlates with improved response and survival in myeloma patients treated with lenalidomide","volume":"120","author":"Klimowicz A.","year":"2012","journal-title":"Blood"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2011.320"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-08-0482"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2012.119"},{"key":"e_1_2_8_15_1","first-page":"3877","article-title":"Alternatively spliced glucocorticoid recep\u2010tor messenger RNAs in glucocorticoid\u2010resistant human multiple myeloma cells","volume":"53","author":"Moalli P.A.","year":"1993","journal-title":"Cancer Research"},{"key":"e_1_2_8_16_1","doi-asserted-by":"crossref","first-page":"8602","DOI":"10.1200\/jco.2009.27.15_suppl.8602","article-title":"Use of alternate splicing to identify subgroups in uniformly treated newly\u2010diagnosed myeloma","volume":"27","author":"Munshi N.C.","year":"2009","journal-title":"Journal of Clinical Oncology"},{"key":"e_1_2_8_17_1","unstructured":"National Cancer Institute Division of Cancer Prevention. (1999)Requirements for pharmacokinetic and biomarker methods development.http:\/\/prevention.cancer.gov\/files\/clinical-trials\/biomarkers.pdf. Accessed September 9 2013."},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2012.04.055"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1103283"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-08-373159"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(13)70380-2"},{"key":"e_1_2_8_22_1","first-page":"194","article-title":"Cereblon expression predicts response, progression free and overall survival after pomalidomide and dexamethasone therapy in multiple myeloma (oral presentation)","volume":"120","author":"Schuster S.R.","year":"2012","journal-title":"Blood (ASH Annual Meeting Abstracts)"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1109016"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10496"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-05-356063"}],"container-title":["British Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbjh.12622","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bjh.12622","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bjh.12622","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bjh.12622","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T00:09:46Z","timestamp":1696291786000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bjh.12622"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,10,28]]},"references-count":24,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2014,1]]}},"alternative-id":["10.1111\/bjh.12622"],"URL":"https:\/\/doi.org\/10.1111\/bjh.12622","archive":["Portico"],"relation":{},"ISSN":["0007-1048","1365-2141"],"issn-type":[{"value":"0007-1048","type":"print"},{"value":"1365-2141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,10,28]]},"assertion":[{"value":"2013-05-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-07-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-10-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}