{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T10:25:48Z","timestamp":1751451948828},"reference-count":23,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,10,29]],"date-time":"2013-10-29T00:00:00Z","timestamp":1383004800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2014,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Immunomodulatory drugs (<jats:styled-content style=\"fixed-case\">IM<\/jats:styled-content>i<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>s) are key components of treatment for hematologic malignancies, especially multiple myeloma (<jats:styled-content style=\"fixed-case\">MM<\/jats:styled-content>). Cereblon (<jats:styled-content style=\"fixed-case\">CRBN<\/jats:styled-content>) expression was described to be essential for the activity of thalidomide. Furthermore, <jats:styled-content style=\"fixed-case\">IM<\/jats:styled-content>i<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content> binding to <jats:styled-content style=\"fixed-case\">CRBN<\/jats:styled-content> is cytotoxic to multiple myeloma cells and absence of <jats:styled-content style=\"fixed-case\">CRBN<\/jats:styled-content> confers <jats:styled-content style=\"fixed-case\">IM<\/jats:styled-content>i<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>s resistance. Interleukin\u20106 (<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106) is a potent pleiotropic cytokine that regulates plasma cell (<jats:styled-content style=\"fixed-case\">PC<\/jats:styled-content>) growth via the <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106 receptor (<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106R). <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106\/<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content> autocrine activity is implicated in the development and progression of cancers including cervical cancer, prostate cancer, and multiple myeloma. The aim of the study was to evaluate <jats:styled-content style=\"fixed-case\">CRBN<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content> expressions and their impact on clinical efficacy of dexamethasone\u2013thalidomide therapy in multiple myeloma (<jats:styled-content style=\"fixed-case\">MM<\/jats:styled-content>) patients, in addition to their association with other clinical and prognostic parameters. Forty\u2010six newly diagnosed <jats:styled-content style=\"fixed-case\">MM<\/jats:styled-content> patients were enrolled in the study. We measured <jats:styled-content style=\"fixed-case\">CRBN<\/jats:styled-content> expression prior to therapy initiation by real\u2010time polymerase chain reaction in 46 bone marrow (<jats:styled-content style=\"fixed-case\">BM<\/jats:styled-content>) aspiration samples of patients and controls. In addition, <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content> expression was evaluated on <jats:styled-content style=\"fixed-case\">BM<\/jats:styled-content> biopsies of patients and controls by immunohistochemistry (<jats:styled-content style=\"fixed-case\">IHC<\/jats:styled-content>). Twenty\u2010eight males (60.9%) and 18 females (39.1%) were enrolled. The mean age was 65.11\u00a0\u00b1\u00a07.3\u00a0yr (range 39\u201377\u00a0yr). Median <jats:styled-content style=\"fixed-case\">CRBN<\/jats:styled-content> expression in 46\u00a0<jats:styled-content style=\"fixed-case\">BM<\/jats:styled-content> samples of <jats:styled-content style=\"fixed-case\">MM<\/jats:styled-content> patients was significantly higher than in controls (<jats:italic>P\u00a0<\/jats:italic>&lt;<jats:italic>\u00a0<\/jats:italic>0.001). Among established prognostic parameters, international staging system (<jats:styled-content style=\"fixed-case\">ISS<\/jats:styled-content>), serum beta\u20102\u2010microglobulin (<jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>2<jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>), and serum albumin correlated reversely with <jats:styled-content style=\"fixed-case\">CRBN<\/jats:styled-content> expression. <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content> expression was significantly higher in patients than in controls. <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content> expression was significantly associated with response to treatment (<jats:italic>P\u00a0<\/jats:italic>&lt;<jats:italic>\u00a0<\/jats:italic>0.001), <jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>2<jats:styled-content style=\"fixed-case\">M<\/jats:styled-content> (<jats:italic>P\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0.032), and <jats:styled-content style=\"fixed-case\">ISS<\/jats:styled-content> (<jats:italic>P\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0.028). Strong intensity expression was associated with low <jats:styled-content style=\"fixed-case\">CRBN<\/jats:styled-content> expression (<jats:italic>P<jats:bold>\u00a0<\/jats:bold><\/jats:italic>=<jats:italic><jats:bold>\u00a0<\/jats:bold><\/jats:italic>0.001).In conclusion, <jats:styled-content style=\"fixed-case\">CRBN<\/jats:styled-content> expression may provide a biomarker to predict response to <jats:styled-content style=\"fixed-case\">IM<\/jats:styled-content>i<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content> in patients with <jats:styled-content style=\"fixed-case\">MM<\/jats:styled-content> and its high expression can serve as a marker of good prognosis. Strong <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content> expression is associated with poor response to therapy in multiple myeloma patients and may be used as a prognostic marker.<\/jats:p>","DOI":"10.1111\/ejh.12207","type":"journal-article","created":{"date-parts":[[2013,10,12]],"date-time":"2013-10-12T01:40:36Z","timestamp":1381542036000},"page":"13-18","source":"Crossref","is-referenced-by-count":11,"title":["Do baseline <scp>C<\/scp>ereblon gene expression and <scp>IL<\/scp>\u20106 receptor expression determine the response to thalidomide\u2013dexamethasone treatment in <scp>M<\/scp>ultiple myeloma patients?"],"prefix":"10.1111","volume":"92","author":[{"given":"Ahmed M. 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