{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:58:22Z","timestamp":1789016302118,"version":"build-2803163510"},"reference-count":30,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,3,12]],"date-time":"2020-03-12T00:00:00Z","timestamp":1583971200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["16ck0106077h0002"],"award-info":[{"award-number":["16ck0106077h0002"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["19ck0106348h0002"],"award-info":[{"award-number":["19ck0106348h0002"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cereblon (CRBN) is a target for immunomodulatory drugs. This study investigated the prognostic value of the expression of CRBN\u2010pathway genes on the clinical relevance of lenalidomide (Len) treatment and evaluated the levels of CRBN\u2010binding proteins and mutations in these genes after Len treatment. Forty\u2010eight primary multiple myeloma cells were collected prior to treatment with Len and dexamethasone (Ld) and 25 paired samples were obtained post\u2010Ld therapy. These tumor cells were used to determine the expression and mutated forms of the CRBN\u2010pathway genes. Following normalization with <jats:italic>CRBN<\/jats:italic> levels, there was a significantly reduced <jats:italic>IKZF1\/CRBN<\/jats:italic> ratio in samples that responded poorly to Ld therapy. Moreover, patients with low ratios of <jats:italic>IKZF1\/CRBN<\/jats:italic> showed a significantly shorter progression\u2010free survival (PFS) and overall survival (OS) than those with higher ratios. However, patients with high ratios of <jats:italic>KPNA2\/CRBN<\/jats:italic> showed a significantly shorter PFS and OS than patients with lower ratios. Of the 25 paired samples analyzed, most samples showed a reduction in the expression of <jats:italic>CRBN<\/jats:italic> and an increase in <jats:italic>IKZF1<\/jats:italic> gene expression. No mutations were observed in <jats:italic>CRBN<\/jats:italic>, <jats:italic>IKZF1<\/jats:italic>, or <jats:italic>CUL4A<\/jats:italic> genes in the post\u2010Ld samples. In conclusion, a decreased expression of <jats:italic>IKZF1<\/jats:italic> and increased expression of <jats:italic>KPNA2<\/jats:italic> compared to that of <jats:italic>CRBN<\/jats:italic> mRNA predicts poor outcomes of Ld therapy.<\/jats:p>","DOI":"10.1111\/cas.14352","type":"journal-article","created":{"date-parts":[[2020,2,15]],"date-time":"2020-02-15T15:44:05Z","timestamp":1581781445000},"page":"1333-1343","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Expression, mutation, and methylation of cereblon\u2010pathway genes at pre\u2010 and post\u2010lenalidomide treatment in multiple myeloma"],"prefix":"10.1111","volume":"111","author":[{"given":"Takuto","family":"Tachita","sequence":"first","affiliation":[{"name":"Department of Hematology and Oncology Nagoya City University Graduate School of Medical Sciences Nagoya Japan"},{"name":"Department of Gastroenterology and Hematology Hirosaki University Graduate 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