{
  "abstract": "Bone marrow homeostasis relies on the interaction between hematopoietic cells and the hematopoietic niche, a balance often compromised in hematological malignancies and conditions of protein malnutrition. Butyrate exhibits immunomodulatory, antineoplastic, and hematopoiesis-regulating properties; however, its effects on leukemic cell behavior under metabolic stress remain poorly understood. Thus, this study evaluated the influence of butyrate on mesenchymal stromal cells and leukemic cells subjected to protein restriction, as well as its impact on clonogenic potential and cellular differentiation. The C3H10T1/2 (mesenchymal stromal cells) and C1498 (murine myeloid leukemia) cell lines were cultured under control conditions (10% fetal bovine serum) or protein restriction (1%) and treated with sodium butyrate, busulfan, or a combination of both. Cell viability (MTT), cell death, and the cell cycle were assessed via flow cytometry. Additionally, C1498 cells were cultured in semi-solid medium (MethoCult®) to evaluate colony formation, colony metabolic activity, and phenotypic characterization (via flow cytometry) of c-Kit⁺, c-Kit⁺Ly6G⁺CD115⁺, and c-Kit⁺CD115⁺ populations, as well as granulocytic (Ly6G⁺) and monocytic (CD115⁺) populations. Stromal cells showed greater resistance to metabolic stress than leukemic cells, while butyrate modulated their viability in a time-dependent manner. In C1498 cells, butyrate significantly reduced clonogenic potential ‒ evidenced by a decrease in the number of colonies and the metabolic activity of the formed colonies ‒ an effect that persisted in the presence of busulfan. Furthermore, it promoted remodeling of the myeloid differentiation profile by increasing the frequency of granulocytes, reducing mature monocytes, and differentially modulating CD107b expression in these populations. Phenotypic characterization revealed a reduction in the frequency of c-Kit⁺ cells, concomitant with an increase in c-Kit⁺Ly6G⁺CD115⁺ and c-Kit⁺CD115⁺ populations compared to busulfan treatment alone, suggesting a butyrate-induced reorganization of the cellular differentiation program. Collectively, these results demonstrate that butyrate exerts effects extending beyond cytotoxicity, reducing clonogenic potential and modulating leukemic cell differentiation under metabolic stress. These findings reinforce its potential as a modulator of leukemic cell behavior and indicate that targeting hematopoietic regulatory mechanisms may represent a promising strategy to optimize antineoplastic therapies and preserve bone marrow homeostasis.",
  "abstract_shown": true,
  "affiliations": [
    "Universidade de São Paulo (USP), São Paulo, SP, Brazil"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Rosana LOPES RODRIGUES AMON"
    },
    {
      "affs": [
        0
      ],
      "name": "Beatriz ALMEIDA"
    },
    {
      "affs": [
        0
      ],
      "name": "Giulia TOSCANO GIANNINI"
    },
    {
      "affs": [
        0
      ],
      "name": "Edson NAOTO MAKIYAMA"
    },
    {
      "affs": [
        0
      ],
      "name": "Ricardo AMBRÓSIO FOCK"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/b25e30yat65vn.bib",
  "cited_by": 0,
  "doi": "10.1016/j.htct.2026.108103",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S253113792601850X",
  "id": "b25e30yat65vn",
  "issns": [
    "2531-1379",
    "2531-1387"
  ],
  "landing_url": "https://doi.org/10.1016/j.htct.2026.108103",
  "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",
      "2720|Acute Myeloid Leukemia Research"
    ]
  ],
  "openalex": "W7223239061",
  "pdf_url": "https://www.sciencedirect.com/science/article/pii/S253113792601850X/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-23",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/b25e30yat65vn.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:43:28Z",
      "native_id": "e0d2a738cc144919aae3cdb71130ca1a",
      "source": "doaj",
      "url": "https://doi.org/10.1016/j.htct.2026.108103"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "lcc:RC633-647.5",
      "subfield": "endocrinology-metabolism"
    }
  ],
  "title": "BEYOND CYTOTOXICITY: BUTYRATE REPROGRAMS DIFFERENTIATION AND REDUCES CLONOGENIC POTENTIAL IN MYELOID LEUKEMIA UNDER METABOLIC STRESS",
  "title_text": "BEYOND CYTOTOXICITY: BUTYRATE REPROGRAMS DIFFERENTIATION AND REDUCES CLONOGENIC POTENTIAL IN MYELOID LEUKEMIA UNDER METABOLIC STRESS",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:43:28Z",
  "url": "https://research.draconitic.com/paper/b25e30yat65vn",
  "venue": "Hematology, Transfusion and Cell Therapy",
  "versions": []
}