{
  "abstract": "Background: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Although cure rates have improved considerably, 20–30% of patients relapse due to chemotherapy resistance. Recent single-cell sequencing studies [1] demonstrated that resistant clones do not emerge through the selection of genetically distinct subclones but rather through transitions between transcriptional states that can become stabilized by epigenetic mechanisms after repeated stress exposure, generating a “transcriptional memory”. Based on this hypothesis, we aim to analyze the transcriptome of B-cell ALL (B-ALL) samples after serial passage and chemotherapy treatment in mice, simulating disease relapse. We will investigate transcriptional changes associated with chemotherapy exposure and correlate them with in vitro drug resistance and patients’ clinical responses, assessed by minimal residual disease on days 8, 15, 33 and 78/96. Methods: Relapse models will be generated using diagnostic samples from 10 pediatric B-ALL cases, including five good and five poor clinical responders. Leukemia-bearing mice will receive vincristine (V), dexamethasone (D), l-asparaginase (L) and daunorubicin (Da). Relapsed samples collected after treatment cycles will be evaluated for resistance to these four drugs. Samples showing increased resistance will also be tested against a panel of 61 antineoplastic agents. Transcriptomic profiles of relapsed leukemias will be compared with matched untreated controls and subsequently between good and poor responder groups. Results: In this initial phase, the induction protocol was standardized using vincristine (0.15 mg/kg, once weekly), dexamethasone (5 mg/kg, five times weekly), asparaginase (1,000 IU/kg, twice weekly) and daunorubicin (1.2 mg/kg, once weekly), with adequate toxicity control. Leukemia progression was monitored weekly by flow cytometric analysis of 50 μL of peripheral blood, quantifying human CD45+ or CD19+ cells relative to murine CD45+ cells. Three of the ten selected B-ALL samples (one good responder and two poor responders) have already completed the protocol until the generation of the proposed transcriptional memory, while the remaining seven are still undergoing induction treatment. Conclusion: The established murine model reproduced differences in treatment response observed in patients. Poor responders exhibited reduced sensitivity to induction therapy, whereas leukemias from good responders also relapsed after a treatment-free period. The next phase will determine whether transcriptional memory is established during relapse, whether it is more frequent in poor responders, and which transcriptomic alterations are associated with chemotherapy resistance.",
  "abstract_shown": true,
  "affiliations": [
    "Centro Infantil Boldrini, Campinas, SP, Brazil"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Manuella Munuera ROSATI"
    },
    {
      "affs": [
        0
      ],
      "name": "Maria Luiza Silva PIRES"
    },
    {
      "affs": [
        0
      ],
      "name": "Juliana Ronchi CORRÊA"
    },
    {
      "affs": [
        0
      ],
      "name": "Amilcar Cardoso AZEVEDO"
    },
    {
      "affs": [
        0
      ],
      "name": "José Andrés YUNES"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fnj10tv30zrbx.bib",
  "cited_by": 0,
  "doi": "10.1016/j.htct.2026.107697",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S2531137926014446",
  "id": "fnj10tv30zrbx",
  "issns": [
    "2531-1379",
    "2531-1387"
  ],
  "landing_url": "https://doi.org/10.1016/j.htct.2026.107697",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RC633-647.5"
    ],
    [
      "openalex",
      "2739|Acute Lymphoblastic Leukemia research"
    ]
  ],
  "openalex": "W7223118742",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-23",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/fnj10tv30zrbx.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:43:27Z",
      "native_id": "aaa0cf106af34b7ba6cc2b57b2cabbbc",
      "source": "doaj",
      "url": "https://doi.org/10.1016/j.htct.2026.107697"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2739|Acute Lymphoblastic Leukemia research",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "TRANSCRIPTIONAL MEMORY AND DRUG RESISTANCE IN PEDIATRIC ACUTE LYMPHOID LEUKEMIA",
  "title_text": "TRANSCRIPTIONAL MEMORY AND DRUG RESISTANCE IN PEDIATRIC ACUTE LYMPHOID LEUKEMIA",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:43:27Z",
  "url": "https://research.draconitic.com/paper/fnj10tv30zrbx",
  "venue": "Hematology, Transfusion and Cell Therapy",
  "versions": []
}