{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T16:52:43Z","timestamp":1792601563470,"version":"4.5.0"},"reference-count":192,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,4,18]],"date-time":"2025-04-18T00:00:00Z","timestamp":1744934400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Acute Myeloid Leukemia (AML) is characterized by aggressive proliferation and metabolic reprogramming that support its survival and resistance to therapy. This review explores the metabolic distinctions between AML cells and normal hematopoietic stem cells (HSCs), emphasizing the role of altered mitochondrial function, oxidative phosphorylation (OXPHOS), and biosynthetic pathways in leukemic progression. AML cells exhibit distinct metabolic vulnerabilities, including increased mitochondrial biogenesis, reliance on glycolysis and amino acid metabolism, and unique signaling interactions that sustain leukemic stem cells (LSCs). These dependencies provide potential therapeutic targets, as metabolic inhibitors have demonstrated efficacy in disrupting AML cell survival while sparing normal hematopoietic cells. We examine current and emerging metabolic therapies, such as inhibitors targeting glycolysis, amino acid metabolism, and lipid biosynthesis, highlighting their potential in overcoming drug resistance. However, challenges remain in translating these strategies into clinical practice due to AML\u2019s heterogeneity and adaptability. Further research into AML\u2019s metabolic plasticity and precision medicine approaches is crucial for improving treatment outcomes. Understanding and exploiting AML\u2019s metabolic vulnerabilities could pave the way for novel, more effective therapeutic strategies.<\/jats:p>","DOI":"10.3390\/cancers17081355","type":"journal-article","created":{"date-parts":[[2025,4,18]],"date-time":"2025-04-18T06:23:56Z","timestamp":1744957436000},"page":"1355","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Understanding and Targeting Metabolic Vulnerabilities in Acute Myeloid Leukemia: An Updated Comprehensive Review"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9224-3813","authenticated-orcid":false,"given":"Sridevi","family":"Addanki","sequence":"first","affiliation":[{"name":"Division of Pediatric Hematology\/Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4084-1277","authenticated-orcid":false,"given":"Lana","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology\/Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Stevens","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology\/Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1182\/asheducation-2004.1.80","article-title":"The molecular basis of leukemia","volume":"1","author":"Gilliland","year":"2004","journal-title":"Hematol. 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