{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:43:08Z","timestamp":1785426188606,"version":"3.56.0"},"posted":{"date-parts":[[2026,6,19]]},"reference-count":69,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T00:00:00Z","timestamp":1781827200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"id":[{"id":"https:\/\/ror.org\/011kf5r70","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Blood Cancer United"},{"name":"Barrie Dalgleish Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Multiple myeloma (MM) is a heterogenous cancer that remains mostly incurable. A unifying feature of MM cells is a highly interconnected network of transcription factors and co-factors that coordinate the activity of super-enhancers to enforce myeloma cell identity. Targeting this network offers a promising avenue for therapeutic intervention across genetically diverse myeloma sub-types. Using integrated molecular and functional genomic approaches we identified Menin as a key driver of oncogenic gene expression in MM cells. Menin and its co-factor KMT2A bind at super-enhancers and maintain expression of essential myeloma genes, including IRF4. We demonstrate that Menin inhibitors, which have recently been approved for treatment of acute myeloid leukaemia, are highly active in myeloma cell lines and\n                  <jats:italic>in vivo<\/jats:italic>\n                  models. Combining Menin inhibitors with other super-enhancer targeting therapies such EP300\/CREBBP inhibitors or immunomodulatory drugs (IMiDs) overcomes epigenetic plasticity in cells resistant to single agent treatment.\n                <\/jats:p>","DOI":"10.64898\/2026.06.17.733047","type":"posted-content","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T10:10:12Z","timestamp":1781863812000},"source":"Crossref","is-referenced-by-count":0,"title":["Menin regulates oncogenic cell identity transcriptional networks in multiple myeloma"],"prefix":"10.64898","author":[{"given":"Emily","family":"Gruber","sequence":"first","affiliation":[{"name":"Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia"},{"name":"Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subhasree","family":"Kumar","sequence":"additional","affiliation":[{"name":"Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia"},{"name":"Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rheana","family":"Franich","sequence":"additional","affiliation":[{"name":"Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany","family":"Khong","sequence":"additional","affiliation":[{"name":"Australian Centre for Blood Diseases, Monash University, Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Neville","sequence":"additional","affiliation":[{"name":"School of Translational Medicine, Monash University, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching-Seng","family":"Ang","sequence":"additional","affiliation":[{"name":"Bio21 Institute, University of Melbourne, Parkville, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"The","sequence":"additional","affiliation":[{"name":"School of Translational Medicine, Monash University, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradon","family":"Rumler","sequence":"additional","affiliation":[{"name":"School of Translational Medicine, Monash University, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shania","family":"Alex","sequence":"additional","affiliation":[{"name":"School of Translational Medicine, Monash University, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Dobbs","sequence":"additional","affiliation":[{"name":"School of Translational Medicine, Monash University, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander C.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia"},{"name":"Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Howitt","sequence":"additional","affiliation":[{"name":"Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia"},{"name":"Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin","family":"Hawkins","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research and Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1523-7388","authenticated-orcid":false,"given":"P. Leif","family":"Bergsagel","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology\/Oncology, Mayo Clinic, Scottsdale, Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Chesi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology\/Oncology, Mayo Clinic, Scottsdale, Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Spencer","sequence":"additional","affiliation":[{"name":"Australian Centre for Blood Diseases, Monash University, Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omer","family":"Gilan","sequence":"additional","affiliation":[{"name":"School of Translational Medicine, Monash University, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lev M.","family":"Kats","sequence":"additional","affiliation":[{"name":"Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia"},{"name":"Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia"},{"name":"Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026062105451219000_2026.06.17.733047v1.1","first-page":"907","volume-title":"J Natl Cancer Inst.","volume":"117","year":"2025"},{"key":"2026062105451219000_2026.06.17.733047v1.2","first-page":"45","volume-title":"Nat Rev Dis Primers","volume":"10","year":"2024"},{"key":"2026062105451219000_2026.06.17.733047v1.3","doi-asserted-by":"crossref","first-page":"e473316","DOI":"10.1200\/EDBK-25-473316","article-title":"Current and future directions of immunotherapies in multiple myeloma","volume":"45","year":"2025","journal-title":"Am Soc Clin Oncol Educ Book"},{"key":"2026062105451219000_2026.06.17.733047v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.03.035"},{"key":"2026062105451219000_2026.06.17.733047v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.09.053"},{"key":"2026062105451219000_2026.06.17.733047v1.6","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.24.13931"},{"key":"2026062105451219000_2026.06.17.733047v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/ng0797-260"},{"key":"2026062105451219000_2026.06.17.733047v1.8","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1182\/blood.V88.2.674.bloodjournal882674","article-title":"Dysregulation of cyclin D1 by translocation into an IgH gamma switch region in two multiple myeloma cell lines. 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