{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T21:22:31Z","timestamp":1793740951700,"version":"4.6.1"},"reference-count":57,"publisher":"American Society of Hematology","issue":"14","license":[{"start":{"date-parts":[[2024,7,24]],"date-time":"2024-07-24T00:00:00Z","timestamp":1721779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,10,3]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>The histone H3 at lysine 27 (H3K27) demethylase lysine demethylase 6A (KDM6A) is a tumor suppressor in multiple cancers, including multiple myeloma (MM). We created isogenic MM cells disrupted for KDM6A and tagged the endogenous protein to facilitate genome-wide studies. KDM6A binds genes associated with immune recognition and cytokine signaling. Most importantly, KDM6A binds and activates NLRC5 and CIITA, which encode regulators of major histocompatibility complex genes. Patient data indicate that NLRC5 and CIITA are downregulated in MM with low KDM6A expression. Chromatin analysis shows that KDM6A binds poised and active enhancers and KDM6A loss led to decreased H3K27ac at enhancers, increased H3K27me3 levels in body of genes bound by KDM6A, and decreased gene expression. Reestablishing histone acetylation with an HDAC3 inhibitor leads to upregulation of major histocompatibility complex expression, offering a strategy to restore immunogenicity of KDM6A-deficient tumors. Loss of Kdm6a in Kirsten rat sarcoma virus (K-RAS)-transformed murine fibroblasts led to increased growth in\u00a0vivo associated with decreased T-cell infiltration.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2024024518","type":"journal-article","created":{"date-parts":[[2024,7,24]],"date-time":"2024-07-24T12:53:11Z","timestamp":1721825591000},"page":"1508-1520","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":22,"title":["KDM6A regulates immune response genes in multiple myeloma"],"prefix":"10.1182","volume":"144","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2236-262X","authenticated-orcid":false,"given":"Daphn\u00e9","family":"Dup\u00e9r\u00e9-Richer","sequence":"first","affiliation":[{"name":"1Division of Hematology\/Oncology, University of Florida Health Cancer Center, University of Florida, Gainesville, 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Ignacio","family":"Mart\u00edn-Subero","sequence":"additional","affiliation":[{"name":"5Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer, Universitat de Barcelona, Barcelona, Spain"},{"name":"7Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer, Barcelona, Spain"},{"name":"8Instituci\u00f3 Catalana de Recerca i Estudis Avan\u00e7ats, Barcelona, Spain"},{"name":"11Departamento de Fundamentos Cl\u00ednicos, Universitat de Barcelona, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2973-5038","authenticated-orcid":false,"given":"Giovanni","family":"Tonon","sequence":"additional","affiliation":[{"name":"9Center for Translational Genomics and Bioinformatics, IRCCS San Raffaele Scientific Institute, Milano, 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