{
  "abstract": "Most acute promyelocytic leukemia (APL), driven by the PML::RARA fusion, are now cured with targeted therapies combining all-trans retinoic acid (ATRA) and arsenic trioxide. Some patients treated with earlier ATRA/chemotherapy regimen developed resistance associated with mutations that most often preclude PML::RARA ATRA-binding. Here, we characterized a subset of clustered mutations associated with ATRA-resistance, but not predicted to affect ATRA binding. Most mutants indeed retained full ligand responsiveness, but displayed a basal super-repressive phenotype which did not result from an increased affinity for known corepressors such as NCoR and SMRT. Our findings suggest these mutations are gain-of-function associated with enhanced interactions with unidentified RARA partners with repressive ability. Similar to ATRA-resistant PLZF::RARA variants, these observations stress the role of persistent transcriptional repression of some retinoic acid target genes in acquired ATRA-resistance.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "name": "Glauce M Barbosa"
    },
    {
      "name": "Hao Yuan"
    },
    {
      "name": "Izabella Tambones"
    },
    {
      "name": "Roland H Stote"
    },
    {
      "name": "Hsin Chieh Wu"
    },
    {
      "name": "Hugues de Thé"
    },
    {
      "name": "Albane Le Maire"
    },
    {
      "name": "Marie-Claude C Geoffroy"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/72ddhqhwm9tgq.bib",
  "cited_by": 1,
  "doi": "10.3324/haematol.2025.300279",
  "fulltext_url": null,
  "id": "72ddhqhwm9tgq",
  "issns": [
    "0390-6078",
    "1592-8721"
  ],
  "landing_url": "https://hal.science/hal-05775581v1",
  "language": "en",
  "licence": "CC-BY-NC-4.0",
  "licence_label": "CC BY-NC 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "openalex",
      "1312|Retinoids in leukemia and cellular processes"
    ]
  ],
  "openalex": "W7202342261",
  "pdf_url": "https://hal.science/hal-05775581/document",
  "pmcid": null,
  "pmid": null,
  "published": "2026-08-13",
  "publisher": "Ferrata Storti Foundation",
  "ris": "https://research.draconitic.com/paper/72ddhqhwm9tgq.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:46Z",
      "native_id": "hal-05775581",
      "source": "hal",
      "url": "https://hal.science/hal-05775581v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Retinoids in leukemia and cellular processes",
      "subfield": "molecular-biology"
    }
  ],
  "title": "ATRA resistance conferred by a clustered subset of hotspot PML::RARA mutations enhancing basal repression rather than precluding transactivation",
  "title_text": "ATRA resistance conferred by a clustered subset of hotspot PML::RARA mutations enhancing basal repression rather than precluding transactivation",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:46Z",
  "url": "https://research.draconitic.com/paper/72ddhqhwm9tgq",
  "venue": "Haematologica",
  "versions": []
}