{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE304nnn/GSE304534/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Genomics"],"species":["Homo sapiens"],"gds_type":["Genome binding/occupancy profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE304534"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Activating RARβ to overcome immunomodulatory drug resistance in t(4;14) human myeloma [ChIP-seq]","description":"The t(4;14) translocation is a high-risk cytogenetic abnormality in multiple myeloma (MM) that results in overexpression of fibroblast growth factor receptor 3 (FGFR3) and enhanced MM proliferation, leading to poor prognosis. Herein, we carried out a high-throughput screen on 1855 Food and Drug Administration (FDA)-approved pharmaceuticals and identified all-trans retinoic acid (ATRA), which alone has no anti-MM effect, as a potent drug that enhances the cytotoxic effects of immunomodulatory drugs (IMiDs) in t(4;14) MM cells. Mechanistically, ATRA activates retinoic acid receptor β (RARβ), which then binds to retinoic acid response elements in the FGFR3 promoter. IMiDs enhanced nuclear translocation of histone deacetylase (HDAC)-5 and 3 by reducing HDAC5 Ser498 phosphorylation levels. RARβ, HDAC5 and HDAC3 formed a co-repressor complex that reduced chromatin accessibility and H3K27 acetylation in FGFR3 promoter, FGFR3 expression, and suppressed phosphoinositide 3-kinase/AKT signaling pathways, leading to more MM cell death. Similarly, CD2314, a selective RARβ agonist, sensitized and resensitized t(4;14) MM cells to IMiDs in vitro and in vivo. Thus, these findings underscore the therapeutic potential of ATRA and RARβ agonists in enhancing the efficacy of IMiD-based treatments for t(4;14) MM and offer a promising strategy to overcome IMiD resistance and improve outcomes in this high-risk subgroup.","dates":{"publication":"2026/07/28"},"accession":"GSE304534","cross_references":{"GSM":["GSM9152253","GSM9152252","GSM9152251","GSM9152247","GSM9152246","GSM9152249","GSM9152248","GSM9152250"],"GPL":["28038"],"GSE":["304534"],"taxon":["Homo sapiens"]}}