{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:25:03Z","timestamp":1787030703127,"version":"build-2736575974"},"reference-count":56,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T00:00:00Z","timestamp":1786838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009447","name":"Leukemia & Lymphoma Society of Canada","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100009447","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/0462yrd97","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008986","name":"University of Guelph","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008986","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/01r7awg59","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background: AML cells can be defined by impairments in glycolytic metabolism, resulting in increased glucose uptake coupled with reduced glycolytic flux. Consequently, cells rely on alternative pathways such as glutamine metabolism to fuel mitochondrial respiration through anapleurosis. AML cells express upregulated levels of glutamine transporters and catabolic enzymes such as solute carrier family 1 member 5 (SLC1A5) and glutaminase 1 (GLS-1), respectively, to support metabolic needs; impairment of glutamine metabolism induces proliferative arrest. Our previous work identified plumbagin (PLB) as a selective activator of pyruvate kinase isoform M2 (PKM2), resulting in increased PKM2 tetrameric protein, impaired PKM2 nuclear translocation and suppressed c-Myc expression. Objective: Therefore, we aimed to investigate whether PLB-mediated PKM2 activation influences glutamine metabolism as a downstream effect of c-Myc suppression in AML. Methods\/Results: AML cell lines treated with PLB were cultured in the presence or absence of glutamine and were compared to cell models with genetically suppressed PKM2 to assess for differences in growth. Spectrophotometric analysis revealed that PLB treatment reduces intracellular glutamine uptake, and immunoblotting indicated suppression of GLS-1 expression, ultimately leading to reduced AML cell proliferation and viability. Supplementation with glutamine partially restored cell growth, indicating that PKM2 modulation is associated with impaired glutamine uptake and utilization. Conclusion: Overall, this study explores the downstream implications of PLB-induced alterations in the c-Myc\/PKM2 axis, expanding the understanding of PKM2\u2019s function beyond glycolysis. The findings presented confirm that PKM2 activation leads to indirect consequences on glutamine metabolism in AML, providing further insight into the mechanisms of PLB-mediated AML cell death.<\/jats:p>","DOI":"10.3390\/metabo16080577","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T11:00:05Z","timestamp":1786964405000},"page":"577","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Plumbagin Is a PKM2 Activator That Modulates Glutamine Metabolism and Dependency in Leukemia"],"prefix":"10.3390","volume":"16","author":[{"given":"Nikolina","family":"Vrdoljak","sequence":"first","affiliation":[{"name":"Department of Food Science, University of Guelph, Guelph, ON N1G 2W1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark D.","family":"Minden","sequence":"additional","affiliation":[{"name":"Princess Margaret Cancer Centre, Ontario Cancer Institute, Toronto, ON M5G 2M9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul A.","family":"Spagnuolo","sequence":"additional","affiliation":[{"name":"Department of Food Science, University of Guelph, Guelph, ON N1G 2W1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1056\/NEJMra1406184","article-title":"Acute Myeloid Leukemia","volume":"373","author":"Weisdorf","year":"2015","journal-title":"N. 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