{
  "abstract": "Background: Acute myeloid leukemia (AML) is genetically diverse with a high unmet clinical need for improved treatment options. Dysregulation of the transcription factor MYC plays a central role in AML progression and therapeutic resistance. (E,E)-bisantrene was recently found to inhibit MYC transcription and downstream activity via G-quadruplex DNA stabilization. This study aimed to evaluate the mechanism of action and preclinical activity of (E,E)-bisantrene in AML. Methods: The in vitro and in vivo activity of (E,E)-bisantrene was determined in a variety of AML models (cell lines, xenograft mouse models, and ex vivo human AML mononuclear cells). Transcriptomic, proteomic and phosphoproteomic analyses were performed after treatment with (E,E)-bisantrene. Analyses of -omics data to identify enriched pathways and upstream regulators were performed. Results: (E,E)-bisantrene demonstrated potent anti-proliferative activity across a panel of AML cell lines, inducing apoptosis and reducing S phase proportions. (E,E)-bisantrene significantly prolonged survival in cell- and patient-derived xenograft models of AML. Mechanistically, RNA-seq and proteomic analysis of MOLM13 and MV4-11 cells treated with (E,E)-bisantrene showed significant reductions in the activity of MYC and E2F, together with the cell cycle regulators CDK1/2/4/5. Transcript and protein levels of MYC were reduced in a dose- and time-dependent manner. TP53 and inflammation-associated transcript signatures were also observed. Conclusion: Anti-proliferative activity of (E,E)-bisantrene in preclinical AML models was associated with a downregulation of MYC, CDK1/2/4/5 and E2F. This study supports the ongoing clinical evaluation of (E,E)-bisantrene in AML where MYC is a clinically relevant driver of disease aggressiveness and therapy resistance.",
  "abstract_shown": true,
  "affiliations": [
    "The University of Newcastle"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 18,
  "authors": [
    {
      "name": "H. C. Murray"
    },
    {
      "name": "K. Miller"
    },
    {
      "name": "J. Brzozowski"
    },
    {
      "name": "D. Kiltschewskij"
    },
    {
      "name": "I. Roy"
    },
    {
      "name": "N. Panicker"
    },
    {
      "name": "A. S. Woldu"
    },
    {
      "name": "B. J. Buckley"
    },
    {
      "name": "M. Messina"
    },
    {
      "name": "C. Penney"
    },
    {
      "name": "P. Cuthbertson"
    },
    {
      "name": "S. Sahni"
    },
    {
      "name": "D. Tillett"
    },
    {
      "name": "M. J. Kelso"
    },
    {
      "name": "J. Sillar"
    },
    {
      "name": "M. J. Cairns"
    },
    {
      "name": "A. Enjeti"
    },
    {
      "affs": [
        0
      ],
      "name": "N. M. Verrills"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fnt3djqvj24c1.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.10.750805",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.10.750805v1.full",
  "id": "fnt3djqvj24c1",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.10.750805v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cancer biology"
    ],
    [
      "openalex",
      "2720|Acute Myeloid Leukemia Research"
    ]
  ],
  "openalex": "W7213470453",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.10.750805v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-10",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/fnt3djqvj24c1.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:22:43Z",
      "native_id": "10.64898/2026.09.10.750805",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.10.750805v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "(E,E)-bisantrene suppresses MYC expression and displays anti-leukemic activity in acute myeloid leukemia",
  "title_text": "(E,E)-bisantrene suppresses MYC expression and displays anti-leukemic activity in acute myeloid leukemia",
  "type": "preprint",
  "updated_at": "2026-10-30T12:22:43Z",
  "url": "https://research.draconitic.com/paper/fnt3djqvj24c1",
  "venue": "bioRxiv",
  "versions": []
}