{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T11:08:09Z","timestamp":1789816089477,"version":"4.0.1"},"reference-count":37,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2024,10,27]],"date-time":"2024-10-27T00:00:00Z","timestamp":1729987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Molecular Bases of Disease Dissemination in Lymphoid Malignancies to Optimize Curative Therapeutic Strategies","award":["5 \u00d7 1000 No. 21198"],"award-info":[{"award-number":["5 \u00d7 1000 No. 21198"]}]},{"name":"Associazione Italiana per la Ricerca sul Cancro Foundation Milan, Italy","award":["5 \u00d7 1000 No. 21198"],"award-info":[{"award-number":["5 \u00d7 1000 No. 21198"]}]},{"name":"AIL Novara Onlus, Novara, Italy","award":["5 \u00d7 1000 No. 21198"],"award-info":[{"award-number":["5 \u00d7 1000 No. 21198"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Acute myeloid leukemia (AML) emerges as one of the most common and fatal leukemias. Treatment of the disease remains highly challenging owing to profound metabolic rewiring mechanisms that confer plasticity to AML cells, ultimately resulting in therapy resistance. Autophagy, a highly conserved lysosomal-driven catabolic process devoted to macromolecular turnover, displays a dichotomous role in AML by suppressing or promoting disease development and progression. Glycolytic metabolism represents a pivotal strategy for AML cells to sustain increasing energy needs related to uncontrolled growth during disease progression. In this study, we tested the hypothesis that a high glycolytic rate and low autophagy flux could represent an advantage for AML cell proliferation and thus be detrimental for patient\u2019s prognosis, and vice versa. TCGA in silico analysis of the AML cohort shows that the high expression of MAP1LC3B (along with that of BECN1 and with low expression of p62\/SQSTM1) and the high expression of BNIP3 (along with that of PRKN and of MAP1LC3B), which together are indicative of increased autophagy and mitophagy, correlate with better prognosis. On the other hand, the high expression of glycolytic markers HK2, PFKM, and PKM correlates with poor prognosis. Most importantly, the association of a low expression of glycolytic markers with a high expression of autophagy\u2013mitophagy markers conferred the longest overall survival for AML patients. Transcriptomic analysis showed that this combined signature correlates with the downregulation of a subset of genes required for the differentiation of myeloid cells, lactate\/pyruvate transporters, and cell cycle progression, in parallel with the upregulation of genes involved in autophagy\/lysosomal trafficking and proteolysis, anti-tumor responses like beta-interferon production, and positive regulation of programmed cell death. Taken together, our data support the view that enhanced autophagy-mitophagy flux together with low glycolytic rate predisposes AML patients to a better clinical outcome, suggesting that autophagy inducers and glucose restrictors may hold potential as adjuvant therapeutics for improving AML management.<\/jats:p>","DOI":"10.3390\/ijms252111527","type":"journal-article","created":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T04:15:02Z","timestamp":1730088902000},"page":"11527","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["High Mitophagy and Low Glycolysis Predict Better Clinical Outcomes in Acute Myeloid Leukemias"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7662-4907","authenticated-orcid":false,"given":"Amreen","family":"Salwa","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Pathology, Department of Health Sciences, Universit\u00e0 del Piemonte Orientale, Via P. Solaroli 17, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7192-9672","authenticated-orcid":false,"given":"Alessandra","family":"Ferraresi","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pathology, Department of Health Sciences, Universit\u00e0 del Piemonte Orientale, Via P. Solaroli 17, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1802-9675","authenticated-orcid":false,"given":"Letizia","family":"Vallino","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pathology, Department of Health Sciences, Universit\u00e0 del Piemonte Orientale, Via P. Solaroli 17, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1012-4106","authenticated-orcid":false,"given":"Chinmay","family":"Maheshwari","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pathology, Department of Health Sciences, Universit\u00e0 del Piemonte Orientale, Via P. Solaroli 17, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Moia","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale, Via P. Solaroli 17, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4681-0151","authenticated-orcid":false,"given":"Gianluca","family":"Gaidano","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale, Via P. Solaroli 17, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5494-3034","authenticated-orcid":false,"given":"Ciro","family":"Isidoro","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pathology, Department of Health Sciences, Universit\u00e0 del Piemonte Orientale, Via P. Solaroli 17, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.1056\/NEJMoa1516192","article-title":"Genomic Classification and Prognosis in Acute Myeloid Leukemia","volume":"374","author":"Papaemmanuil","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Roman Diaz, J.L., Vazquez Martinez, M., and Khimani, F. (2024). New Approaches for the Treatment of AML beyond the 7+3 Regimen: Current Concepts and New Approaches. 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