{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:56:27Z","timestamp":1785426987568,"version":"3.56.0"},"posted":{"date-parts":[[2025,11,14]]},"group-title":"Cancer Biology","reference-count":48,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T00:00:00Z","timestamp":1763078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["K08 CA256489"],"award-info":[{"award-number":["K08 CA256489"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01 CA193994"],"award-info":[{"award-number":["R01 CA193994"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["U54 CA196519"],"award-info":[{"award-number":["U54 CA196519"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"award":["6612-20"],"award-info":[{"award-number":["6612-20"]}],"id":[{"id":"https:\/\/ror.org\/04m0xav37","id-type":"ROR","asserted-by":"publisher"}]},{"award":["430255"],"award-info":[{"award-number":["430255"]}],"id":[{"id":"https:\/\/ror.org\/03h1gea69","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,11,14]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Adult and pediatric acute myeloid leukemias (AMLs) harbor distinct mutational profiles, including a higher incidence of\n                  <jats:italic>RAS<\/jats:italic>\n                  and other signaling mutations in young patients. Here we show that the BET inhibitor PLX51107 potently suppresses the growth of\n                  <jats:italic>NRAS<\/jats:italic>\n                  -mutant AML cell lines, and that these activities are enhanced by co-treatment with the MEK inhibitor PD0325901. Controlled preclinical trials in primary mouse\n                  <jats:italic>Nras<\/jats:italic>\n                  -mutant AMLs revealed single agent efficacy of PLX51107 that was enhanced by PD0325901. Leukemias that relapsed during treatment developed intrinsic drug resistance characterized by transition to a more primitive state, up-regulation of Myc target genes, and down-regulation of Ras-associated transcriptional programs. AMLs that relapsed after frontline chemotherapy showed similar transcriptional remodeling. These studies demonstrate transcriptional plasticity in primary AMLs that relapse following\n                  <jats:italic>in vivo<\/jats:italic>\n                  treatment with either targeted agents or chemotherapy, and support evaluating BET inhibition in leukemias with monocytic differentiation and\n                  <jats:italic>RAS<\/jats:italic>\n                  mutations.\n                <\/jats:p>","DOI":"10.1101\/2025.11.13.688312","type":"posted-content","created":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T22:20:16Z","timestamp":1763158816000},"source":"Crossref","is-referenced-by-count":0,"title":["Acute Myeloid Leukemia Relapse after Bromodomain Inhibitor Treatment or Chemotherapy is Characterized by Myc-Ras Transcriptional Remodeling"],"prefix":"10.64898","author":[{"given":"Benjamin 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