{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T05:16:18Z","timestamp":1788498978262,"version":"build-2803163510"},"reference-count":130,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Acute myeloid leukemia (AML) represents a heterogeneous group of hematological malignancies characterized by uncontrolled proliferation of myeloid progenitors and accumulation of immature blasts in the bone marrow. Metabolic reprogramming is now recognized as a core hallmark of AML, generating dependencies that distinguish leukemic cells from normal hematopoietic stem and progenitor cells and that can be exploited therapeutically. In this review we follow a single connected line of argument: we first place metabolic rewiring within the broader hallmarks of cancer, then describe the principal metabolic programs altered in AML and the specific features that distinguish AML from other malignancies. We next examine the inhibitors and drugs that target each of these pathways, linking every drug class to its mechanism of synergy with chemotherapy, the preclinical and clinical evidence available, and its association with outcome in AML. We then consider multi-target (combination) therapy as a distinct opportunity, and finally the principal challenges that remainsafety and tolerability, the metabolic heterogeneity and plasticity of AML, and the design of biomarker-guided trials. Multiple classes of metabolic drugs are discussed, including glycolysis inhibitors, oxidative phosphorylation inhibitors, glutamine metabolism antagonists, fatty acid oxidation modulators, and redox-active compounds. Despite significant challenges, targeting cellular metabolism represents a promising strategy to enhance therapeutic outcomes in patients with AML.<\/jats:p>","DOI":"10.3390\/ph19091384","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T15:08:43Z","timestamp":1788275323000},"page":"1384","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploiting Metabolic Vulnerabilities in Acute Myeloid Leukemia: Rationale and Evidence for Combining Metabolic Modulators with Conventional Chemotherapy"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9992-0664","authenticated-orcid":false,"given":"Usman Ali","family":"Shams","sequence":"first","affiliation":[{"name":"Department of Hematology, University of Health Sciences, Lahore 54000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4333-5850","authenticated-orcid":false,"given":"Fawad","family":"Inayat","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Abdul Wali Khan University, Mardan 23200, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5917-2278","authenticated-orcid":false,"given":"Muhammad Asif","family":"Zeb","sequence":"additional","affiliation":[{"name":"Institute of Paramedical Sciences, Khyber Medical University, Peshawar 25000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2697-7325","authenticated-orcid":false,"family":"Maryam","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Islamia College University, Peshawar 25000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7792-1180","authenticated-orcid":false,"given":"Sulaiman","family":"Shams","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Abdul Wali Khan University, Mardan 23200, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9586-8432","authenticated-orcid":false,"given":"Muhammad Jawad","family":"Ullah","sequence":"additional","affiliation":[{"name":"Department of Allied Health Sciences, Iqra National University, Peshawar 25000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6590-9712","authenticated-orcid":false,"given":"Silvia","family":"Jim\u00e9nez-Morales","sequence":"additional","affiliation":[{"name":"Laboratorio de Innovaci\u00f3n y Medicina de Precisi\u00f3n, N\u00facleo A, Instituto Nacional de Medicina Gen\u00f3mica, Mexico City 14610, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"310","DOI":"10.14740\/jocmr5205","article-title":"Mapping the Grounds for Mortalities in Acute Myeloid Leukemia Through Registry Analyses: A Retrospective Cohort Study of Children, Adolescents, and Young Adults Patients","volume":"16","author":"Elgenidy","year":"2024","journal-title":"J. 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