{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:03:33Z","timestamp":1791396213478,"version":"4.3.3"},"reference-count":176,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:00:00Z","timestamp":1772755200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000048","name":"AMERICAN CANCER SOCIETY","doi-asserted-by":"publisher","award":["RSG-23-1025480-01-IBCD"],"award-info":[{"award-number":["RSG-23-1025480-01-IBCD"]}],"id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004917","name":"CANCER PREVENTION & RESEARCH INSTITUTE OF TEXAS","doi-asserted-by":"publisher","award":["RP210153"],"award-info":[{"award-number":["RP210153"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Acute myeloid leukemia (AML) remains a therapeutically challenging malignancy due to high relapse rates driven by leukemic stem cells (LSCs) and adaptive resistance mechanisms. Emerging evidence positions autophagy as a central regulator of AML pathobiology, exerting context-dependent effects that suppress leukemogenesis during disease initiation yet sustain LSC survival and chemoresistance in established AML. Mechanistically, autophagy integrates mitochondrial quality control, lipid droplet turnover, and metabolic rewiring to support oxidative phosphorylation, particularly under hypoxic bone marrow conditions. Lipophagy-driven fatty acid oxidation has emerged as a key metabolic vulnerability distinguishing LSCs from normal hematopoietic stem cells. Furthermore, non-coding RNAs critically modulate autophagy networks, reinforcing therapy resistance. Preclinical and clinical studies demonstrate that both inhibition and activation of autophagy may yield therapeutic benefit depending on genetic context, mutational landscape, and disease stage. We propose that integrating multi-omics approaches, particularly lipidomics, with artificial intelligence and machine learning will enable precise identification of autophagy-dependent AML subsets. Rational, biomarker-guided modulation of autophagy may overcome resistance while preserving normal hematopoiesis, offering a path toward personalized metabolic targeting in AML.<\/jats:p>","DOI":"10.3390\/life16030428","type":"journal-article","created":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T09:22:14Z","timestamp":1772788934000},"page":"428","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Autophagy and Lipid Metabolism as a Therapeutic Target for Overcoming Drug Resistance in Acute Myeloid Leukemia"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5246-7847","authenticated-orcid":false,"given":"Seyed Mohammadreza","family":"Bolandi","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Karaj Branch, Islamic Azad University, Karaj 3149968111, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2404-5591","authenticated-orcid":false,"given":"Mahdi","family":"Pakjoo","sequence":"additional","affiliation":[{"name":"ATMP Department, Breath Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran 1517964311, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7103-8581","authenticated-orcid":false,"given":"Briandy","family":"Fernandez-Marrero","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, College of Science, The University of Texas at El Paso, El Paso, TX 79968, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir Reza","family":"Boskabadi","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erfan Mohammadi","family":"Sephavand","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Karaj Branch, Islamic Azad University, Karaj 3149968111, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6961-7311","authenticated-orcid":false,"given":"Jamshid Sorouri","family":"Khorashad","sequence":"additional","affiliation":[{"name":"Department of Immunology and Inflammation, Imperial College London, London W12 0NN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5948-508X","authenticated-orcid":false,"given":"Saeid","family":"Ghavami","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy and Cell Science, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3T 2N2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6533-9150","authenticated-orcid":false,"given":"Anna M.","family":"Eiring","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, College of Science, The University of Texas at El Paso, El Paso, TX 79968, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Marchand, T., and Pinho, S. 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