{
  "abstract": "B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is characterized by impaired B-cell maturation and poor prognosis in relapsed/refractory (R/R) cases. While CD20-targeted immunotherapies offer clinical benefit, their efficacy is limited by low and heterogeneous CD20 expression on BCP-ALL cells. In this study, we demonstrate that overexpression of wild-type IKZF1, a tumor suppressor frequently mutated in high-risk BCP-ALL, upregulates CD20 and promotes leukemic B cell maturation. Using a transcriptional mimicry approach, we identified mTORC1 inhibitors as compounds showing similarity to selected IKZF1-induced transcriptional signatures, including convergence on B-cell maturation and induction of CD20 expression both in vitro and in vivo. mTORC1 inhibition enhanced the antitumor efficacy of anti-CD20 monoclonal antibodies and promoted B-lineage antigen expression, while downregulating immature markers. Mechanistically, CD20 upregulation was mediated via the AKT–FOXO1 axis, with AKT phosphorylation being essential for this effect. Importantly, this phenotypic shift was observed in BCP-ALL models with IKZF1 deletions, highlighting the relevance to high-risk disease. Our findings support the use of mTORC1 inhibitors to sensitize BCP-ALL cells to CD20-directed immunotherapies and provide a strong rationale for their clinical evaluation as adjuncts to anti-CD20 immunotherapy in BCP-ALL.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Immunology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland",
    "Doctoral School of Translational Medicine, Centre of Postgraduate Medical Education, Warsaw, Poland",
    "Department of Genetic Predisposition to Cancer, Medical University of Lodz, Lodz, Poland",
    "Department of Pathology, Medical University of Warsaw, Warsaw, Poland",
    "Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, Poland",
    "Josep Carreras Leukaemia Research Institute (IJC), Barcelona, Spain",
    "Red Española de Terapias Avanzadas (TERAV), Instituto de Salud Carlos III (ISCIII), Barcelona, Spain",
    "Hugh and Josseline Langmuir Centre for Myeloma Research, Centre for Haematology, Department of Immunology and Inflammation, Imperial College London, London, UK",
    "Institute of Physiological Chemistry, University of Ulm, Ulm, Germany",
    "Department of Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 17,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Agnieszka Dąbkowska",
      "orcid": "0000-0001-8641-5677"
    },
    {
      "affs": [
        0
      ],
      "name": "Martyna Janowska",
      "orcid": "0000-0002-8703-5614"
    },
    {
      "affs": [
        2
      ],
      "name": "Agata Pastorczak"
    },
    {
      "affs": [
        0,
        1,
        3
      ],
      "name": "Krzysztof Domka",
      "orcid": "0000-0002-2856-6968"
    },
    {
      "affs": [
        4
      ],
      "name": "Zuzanna Nowicka",
      "orcid": "0000-0001-7814-5830"
    },
    {
      "affs": [
        2
      ],
      "name": "Zuzanna Urbanska",
      "orcid": "0000-0002-4810-6627"
    },
    {
      "affs": [
        0
      ],
      "name": "Weronika Zając"
    },
    {
      "affs": [
        0
      ],
      "name": "Mikołaj Bugajewski",
      "orcid": "0009-0009-8043-0716"
    },
    {
      "affs": [
        0
      ],
      "name": "Julia Grzybowska",
      "orcid": "0009-0006-4600-5909"
    },
    {
      "affs": [
        0
      ],
      "name": "Pola Pruchniak",
      "orcid": "0009-0004-8199-2263"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Klaudyna Fidyt"
    },
    {
      "affs": [
        2
      ],
      "name": "Wojciech Fendler"
    },
    {
      "affs": [
        7
      ],
      "name": "Jason Taslim"
    },
    {
      "affs": [
        7
      ],
      "name": "Nicholas T. Crump",
      "orcid": "0000-0001-9610-6763"
    },
    {
      "affs": [
        8
      ],
      "name": "Alexey Ushmorov",
      "orcid": "0000-0003-3724-7253"
    },
    {
      "affs": [
        9
      ],
      "name": "Elzbieta Patkowska"
    },
    {
      "affs": [
        0
      ],
      "name": "Malgorzata Firczuk",
      "orcid": "0000-0002-1719-5233"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dr3haa188bsck.bib",
  "cited_by": 0,
  "doi": "10.1038/s41375-026-03093-z",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13713584/",
  "id": "dr3haa188bsck",
  "issns": [
    "0887-6924",
    "1476-5551"
  ],
  "landing_url": "https://doi.org/10.1038/s41375-026-03093-z",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "2739|Acute Lymphoblastic Leukemia research"
    ]
  ],
  "openalex": "W7203785976",
  "pdf_url": "https://www.nature.com/articles/s41375-026-03093-z.pdf",
  "pmcid": "PMC13713584",
  "pmid": "42618701",
  "published": "2026-08-19",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/dr3haa188bsck.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:24:06Z",
      "native_id": "PMC13713584",
      "source": "pmc",
      "url": "https://doi.org/10.1038/s41375-026-03093-z"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2739|Acute Lymphoblastic Leukemia research",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "mTORC1 inhibition upregulates CD20 and enhances anti-CD20 antibody efficacy in B-cell precursor acute lymphoblastic leukemia",
  "title_text": "mTORC1 inhibition upregulates CD20 and enhances anti-CD20 antibody efficacy in B-cell precursor acute lymphoblastic leukemia",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:21:14Z",
  "url": "https://research.draconitic.com/paper/dr3haa188bsck",
  "venue": "Leukemia",
  "versions": []
}