{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,8]],"date-time":"2026-11-08T03:41:04Z","timestamp":1794109264402,"version":"4.8.0"},"reference-count":68,"publisher":"American Society of Hematology","issue":"11","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,3,13]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Immunomodulatory drugs (IMiDs) are a major class of drugs for treating multiple myeloma (MM); however, acquired resistance to IMiDs remains a significant clinical challenge. Although alterations in cereblon and its pathway are known to contribute to IMiD resistance, they account for only 20% to 30% of cases, and the underlying mechanisms in the majority of the resistance cases remain unclear. Here, we identified adenosine deaminase acting on RNA1 (ADAR1) as a novel driver of lenalidomide resistance in MM. We showed that lenalidomide activates the MDA5-mediated double-stranded RNA (dsRNA)\u2013sensing pathway in MM cells, leading to interferon (IFN)-mediated apoptosis, with ADAR1 as the key regulator. Mechanistically, ADAR1 loss increased lenalidomide sensitivity through endogenous dsRNA accumulation, which in turn triggered dsRNA-sensing pathways and enhanced IFN responses. Conversely, ADAR1 overexpression reduced lenalidomide sensitivity, attributed to increased RNA editing frequency, reduced dsRNA accumulation, and suppression of the dsRNA-sensing pathways. In summary, we report the involvement of ADAR1-regulated dsRNA sensing in modulating lenalidomide sensitivity in MM. These findings highlight a novel RNA-related mechanism underlying lenalidomide resistance and underscore the potential of targeting ADAR1 as a novel therapeutic strategy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2024024429","type":"journal-article","created":{"date-parts":[[2024,12,9]],"date-time":"2024-12-09T15:22:02Z","timestamp":1733757722000},"page":"1164-1181","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":7,"title":["The ADAR1-regulated cytoplasmic dsRNA-sensing pathway is a novel mechanism of lenalidomide resistance in multiple myeloma"],"prefix":"10.1182","volume":"145","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1343-0635","authenticated-orcid":false,"given":"Mun Yee","family":"Koh","sequence":"first","affiliation":[{"name":"1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1737-6322","authenticated-orcid":false,"given":"Tae-Hoon","family":"Chung","sequence":"additional","affiliation":[{"name":"1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2147-790X","authenticated-orcid":false,"given":"Nicole Xin Ning","family":"Tang","sequence":"additional","affiliation":[{"name":"1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9206-2036","authenticated-orcid":false,"given":"Sabrina Hui Min","family":"Toh","sequence":"additional","affiliation":[{"name":"1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5679-671X","authenticated-orcid":false,"given":"Jianbiao","family":"Zhou","sequence":"additional","affiliation":[{"name":"1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1623-615X","authenticated-orcid":false,"given":"Tze King","family":"Tan","sequence":"additional","affiliation":[{"name":"1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1987-3878","authenticated-orcid":false,"given":"Leilei","family":"Chen","sequence":"additional","affiliation":[{"name":"1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore"},{"name":"2Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2578-8335","authenticated-orcid":false,"given":"Wee Joo","family":"Chng","sequence":"additional","affiliation":[{"name":"1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore"},{"name":"3Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore"},{"name":"4Department of Hematology-Oncology, National University Cancer Institute, National University Health System, Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8350-1641","authenticated-orcid":false,"given":"Phaik Ju","family":"Teoh","sequence":"additional","affiliation":[{"name":"1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore"},{"name":"3Department of Medicine, Yong 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