{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,22]],"date-time":"2026-03-22T05:58:42Z","timestamp":1774159122915,"version":"3.50.1"},"reference-count":118,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T00:00:00Z","timestamp":1773964800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto de Investiga\u00e7\u00e3o em Imunologia"},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"crossref","award":["408685\/2024-7"],"award-info":[{"award-number":["408685\/2024-7"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"crossref","award":["2025\/26983-8"],"award-info":[{"award-number":["2025\/26983-8"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>7-ketocholesterol (7-KC) is a bioactive oxysterol generated under oxidative stress and may contribute to bone marrow niche reprogramming in acute myeloid leukemia (AML), thereby promoting stress tolerance and therapeutic resistance Bone marrow mesenchymal stromal cells (MSCs) from healthy donors and AML patients were exposed to subtoxic 7-KC concentrations for 24 h. We evaluated the ABC transporters involved in lipid transport, multidrug resistance and membrane microdomain remodeling; Hedgehog pathway proteins; stress\u2013survival signaling; redox balance by glutathione measurements, and mitochondrial function and dynamics, including membrane potential and gene expression of mitochondrial fission and fusion regulators. Results were integrated using principal component analysis (PCA), heatmaps, and correlation-based networks. Multivariate analyses revealed an integrated, lineage-dependent response. Healthy donor MSCs showed greater plasticity of the efflux and microdomain axis and higher oxidative and mitochondrial vulnerability at high 7-KC doses. AML-MSCs exhibited a basal preconditioned state phenotype and preferentially routed the response toward Hedgehog and stress\u2013survival modules, accompanied by glutathione expansion and adaptive mitochondrial remodeling. 7-KC acts as a broad modulator of several MSC functions, linking sterol homeostasis to Hedgehog signaling, stress\u2013survival pathways, redox balance, and mitochondrial remodeling, potentially supporting a pro-survival, more therapy-tolerant leukemic niche.<\/jats:p>","DOI":"10.3390\/ijms27062842","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T17:02:43Z","timestamp":1774026163000},"page":"2842","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["7-Ketocholesterol Links Sterol Homeostasis to Hedgehog Signaling and Stress\u2013Survival Responses in MSCs from Patients with Acute Myeloid Leukemia"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4327-3928","authenticated-orcid":false,"given":"Cadiele Oliana","family":"Reichert","sequence":"first","affiliation":[{"name":"Lipids, Oxidation and Cell Biology Team, Laboratory of Immunology (LIM19), Heart Institute (InCor), Faculdade de Medicina, Universidade de Sao Paulo-HCFMUSP, Sao Paulo 05403-010, Brazil"},{"name":"Real-World Evidence & Precision Public Health Team, Laboratory of Pathogenesis and Directed Therapy in Onco-Immuno-Hematology (LIM-31), Department of Hematology, Hemotherapy, and Cell Therapy, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo 05419-000, Brazil"},{"name":"Laboratory of Pathogenesis and Directed Therapy in Onco-Immuno-Hematology (LIM-31), Department of Hematology, Hemotherapy, and Cell Therapy, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo 05419-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7492-997X","authenticated-orcid":false,"given":"D\u00e9bora","family":"Levy","sequence":"additional","affiliation":[{"name":"Lipids, Oxidation and Cell Biology Team, Laboratory of Immunology (LIM19), Heart Institute (InCor), Faculdade de Medicina, Universidade de Sao Paulo-HCFMUSP, Sao Paulo 05403-010, Brazil"},{"name":"Instituto de Investiga\u00e7\u00e3o em Imunologia (INCT-iii), CNPq, Sao Paulo 05403-010, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5745-7843","authenticated-orcid":false,"given":"F\u00e1bio Alessandro de","family":"Freitas","sequence":"additional","affiliation":[{"name":"Lipids, Oxidation and Cell Biology Team, Laboratory of Immunology (LIM19), Heart Institute (InCor), Faculdade de Medicina, Universidade de Sao Paulo-HCFMUSP, Sao Paulo 05403-010, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliana Sampaio","family":"Silva","sequence":"additional","affiliation":[{"name":"Lipids, Oxidation and Cell Biology Team, Laboratory of Immunology (LIM19), Heart Institute (InCor), Faculdade de Medicina, Universidade de Sao Paulo-HCFMUSP, Sao Paulo 05403-010, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3222-9990","authenticated-orcid":false,"given":"Priscila de Lima","family":"Barros","sequence":"additional","affiliation":[{"name":"Lipids, Oxidation and Cell Biology Team, Laboratory of Immunology (LIM19), Heart Institute (InCor), Faculdade de Medicina, Universidade de Sao Paulo-HCFMUSP, Sao Paulo 05403-010, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00e9ssica Liliane","family":"Paz","sequence":"additional","affiliation":[{"name":"Lipids, Oxidation and Cell Biology Team, Laboratory of Immunology (LIM19), Heart Institute 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