{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T01:39:58Z","timestamp":1769823598205,"version":"3.49.0"},"reference-count":47,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,3,22]],"date-time":"2024-03-22T00:00:00Z","timestamp":1711065600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Foundation for Science and Technology","award":["UIDB\/50026\/2020"],"award-info":[{"award-number":["UIDB\/50026\/2020"]}]},{"name":"Foundation for Science and Technology","award":["UIDP\/50026\/2020"],"award-info":[{"award-number":["UIDP\/50026\/2020"]}]},{"name":"Foundation for Science and Technology","award":["NORTE-01-0145-FEDER-000039"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-000039"]}]},{"name":"Foundation for Science and Technology","award":["NORTE-01-0145-FEDER-000055"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-000055"]}]},{"name":"Foundation for Science and Technology","award":["UID\/BIA\/ 04050\/2020"],"award-info":[{"award-number":["UID\/BIA\/ 04050\/2020"]}]},{"name":"Foundation for Science and Technology","award":["LA\/P\/0069\/2020"],"award-info":[{"award-number":["LA\/P\/0069\/2020"]}]},{"name":"Foundation for Science and Technology","award":["SFRH\/BD\/146065\/2019"],"award-info":[{"award-number":["SFRH\/BD\/146065\/2019"]}]},{"name":"Foundation for Science and Technology","award":["SFRH\/BD\/145955\/2019"],"award-info":[{"award-number":["SFRH\/BD\/145955\/2019"]}]},{"name":"Foundation for Science and Technology","award":["COVID\/BD\/153456\/2023"],"award-info":[{"award-number":["COVID\/BD\/153456\/2023"]}]},{"name":"Norte Portugal Regional Operational Programme","award":["UIDB\/50026\/2020"],"award-info":[{"award-number":["UIDB\/50026\/2020"]}]},{"name":"Norte Portugal Regional Operational Programme","award":["UIDP\/50026\/2020"],"award-info":[{"award-number":["UIDP\/50026\/2020"]}]},{"name":"Norte Portugal Regional Operational Programme","award":["NORTE-01-0145-FEDER-000039"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-000039"]}]},{"name":"Norte Portugal Regional Operational Programme","award":["NORTE-01-0145-FEDER-000055"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-000055"]}]},{"name":"Norte Portugal Regional Operational Programme","award":["UID\/BIA\/ 04050\/2020"],"award-info":[{"award-number":["UID\/BIA\/ 04050\/2020"]}]},{"name":"Norte Portugal Regional Operational Programme","award":["LA\/P\/0069\/2020"],"award-info":[{"award-number":["LA\/P\/0069\/2020"]}]},{"name":"Norte Portugal Regional Operational Programme","award":["SFRH\/BD\/146065\/2019"],"award-info":[{"award-number":["SFRH\/BD\/146065\/2019"]}]},{"name":"Norte Portugal Regional Operational Programme","award":["SFRH\/BD\/145955\/2019"],"award-info":[{"award-number":["SFRH\/BD\/145955\/2019"]}]},{"name":"Norte Portugal Regional Operational Programme","award":["COVID\/BD\/153456\/2023"],"award-info":[{"award-number":["COVID\/BD\/153456\/2023"]}]},{"name":"Strategic Programme","award":["UIDB\/50026\/2020"],"award-info":[{"award-number":["UIDB\/50026\/2020"]}]},{"name":"Strategic Programme","award":["UIDP\/50026\/2020"],"award-info":[{"award-number":["UIDP\/50026\/2020"]}]},{"name":"Strategic Programme","award":["NORTE-01-0145-FEDER-000039"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-000039"]}]},{"name":"Strategic Programme","award":["NORTE-01-0145-FEDER-000055"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-000055"]}]},{"name":"Strategic Programme","award":["UID\/BIA\/ 04050\/2020"],"award-info":[{"award-number":["UID\/BIA\/ 04050\/2020"]}]},{"name":"Strategic Programme","award":["LA\/P\/0069\/2020"],"award-info":[{"award-number":["LA\/P\/0069\/2020"]}]},{"name":"Strategic Programme","award":["SFRH\/BD\/146065\/2019"],"award-info":[{"award-number":["SFRH\/BD\/146065\/2019"]}]},{"name":"Strategic Programme","award":["SFRH\/BD\/145955\/2019"],"award-info":[{"award-number":["SFRH\/BD\/145955\/2019"]}]},{"name":"Strategic Programme","award":["COVID\/BD\/153456\/2023"],"award-info":[{"award-number":["COVID\/BD\/153456\/2023"]}]},{"name":"NewG Lab Pharma","award":["UIDB\/50026\/2020"],"award-info":[{"award-number":["UIDB\/50026\/2020"]}]},{"name":"NewG Lab Pharma","award":["UIDP\/50026\/2020"],"award-info":[{"award-number":["UIDP\/50026\/2020"]}]},{"name":"NewG Lab Pharma","award":["NORTE-01-0145-FEDER-000039"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-000039"]}]},{"name":"NewG Lab Pharma","award":["NORTE-01-0145-FEDER-000055"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-000055"]}]},{"name":"NewG Lab Pharma","award":["UID\/BIA\/ 04050\/2020"],"award-info":[{"award-number":["UID\/BIA\/ 04050\/2020"]}]},{"name":"NewG Lab Pharma","award":["LA\/P\/0069\/2020"],"award-info":[{"award-number":["LA\/P\/0069\/2020"]}]},{"name":"NewG Lab Pharma","award":["SFRH\/BD\/146065\/2019"],"award-info":[{"award-number":["SFRH\/BD\/146065\/2019"]}]},{"name":"NewG Lab Pharma","award":["SFRH\/BD\/145955\/2019"],"award-info":[{"award-number":["SFRH\/BD\/145955\/2019"]}]},{"name":"NewG Lab Pharma","award":["COVID\/BD\/153456\/2023"],"award-info":[{"award-number":["COVID\/BD\/153456\/2023"]}]},{"name":"FCT fellowship","award":["UIDB\/50026\/2020"],"award-info":[{"award-number":["UIDB\/50026\/2020"]}]},{"name":"FCT fellowship","award":["UIDP\/50026\/2020"],"award-info":[{"award-number":["UIDP\/50026\/2020"]}]},{"name":"FCT fellowship","award":["NORTE-01-0145-FEDER-000039"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-000039"]}]},{"name":"FCT fellowship","award":["NORTE-01-0145-FEDER-000055"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-000055"]}]},{"name":"FCT fellowship","award":["UID\/BIA\/ 04050\/2020"],"award-info":[{"award-number":["UID\/BIA\/ 04050\/2020"]}]},{"name":"FCT fellowship","award":["LA\/P\/0069\/2020"],"award-info":[{"award-number":["LA\/P\/0069\/2020"]}]},{"name":"FCT fellowship","award":["SFRH\/BD\/146065\/2019"],"award-info":[{"award-number":["SFRH\/BD\/146065\/2019"]}]},{"name":"FCT fellowship","award":["SFRH\/BD\/145955\/2019"],"award-info":[{"award-number":["SFRH\/BD\/145955\/2019"]}]},{"name":"FCT fellowship","award":["COVID\/BD\/153456\/2023"],"award-info":[{"award-number":["COVID\/BD\/153456\/2023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Altered glycolytic metabolism has been associated with chemoresistance in acute myeloid leukemia (AML). However, there are still aspects that need clarification, as well as how to explore these metabolic alterations in therapy. In the present study, we aimed to elucidate the role of glucose metabolism in the acquired resistance of AML cells to cytarabine (Ara-C) and to explore it as a therapeutic target. Resistance was induced by stepwise exposure of AML cells to increasing concentrations of Ara-C. Ara-C-resistant cells were characterized for their growth capacity, genetic alterations, metabolic profile, and sensitivity to different metabolic inhibitors. Ara-C-resistant AML cell lines, KG-1 Ara-R, and MOLM13 Ara-R presented different metabolic profiles. KG-1 Ara-R cells exhibited a more pronounced glycolytic phenotype than parental cells, with a weaker acute response to 3-bromopyruvate (3-BP) but higher sensitivity after 48 h. KG-1 Ara-R cells also display increased respiration rates and are more sensitive to phenformin than parental cells. On the other hand, MOLM13 Ara-R cells display a glucose metabolism profile similar to parental cells, as well as sensitivity to glycolytic inhibitors. These results indicate that acquired resistance to Ara-C in AML may involve metabolic adaptations, which can be explored therapeutically in the AML patient setting who developed resistance to therapy.<\/jats:p>","DOI":"10.3390\/pharmaceutics16040442","type":"journal-article","created":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T12:50:49Z","timestamp":1711371049000},"page":"442","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Glucose Metabolism as a Potential Therapeutic Target in Cytarabine-Resistant Acute Myeloid Leukemia"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5413-3445","authenticated-orcid":false,"given":"Joana","family":"Pereira-Vieira","sequence":"first","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, Braga\/Guimar\u00e3es, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9825-6674","authenticated-orcid":false,"given":"Daniela D.","family":"Weber","sequence":"additional","affiliation":[{"name":"Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, University Hospital of the Paracelsus Medical University, 5020 Salzburg, Austria"}]},{"given":"S\u00e2mia","family":"Silva","sequence":"additional","affiliation":[{"name":"Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos 14784-400, SP, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1031-4241","authenticated-orcid":false,"given":"Catarina","family":"Barbosa-Matos","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, Braga\/Guimar\u00e3es, Portugal"}]},{"given":"Sara","family":"Granja","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, Braga\/Guimar\u00e3es, Portugal"},{"name":"Department of Pathological, Cytological and Thanatological Anatomy, ESS|P.PORTO, 4200-072 Porto, Portugal"},{"name":"REQUIMTE\/LAQV, Escola Superior de Sa\u00fade, Instituto Polit\u00e9cnico do Porto, Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9639-7940","authenticated-orcid":false,"given":"Rui Manuel","family":"Reis","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, Braga\/Guimar\u00e3es, Portugal"},{"name":"Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos 14784-400, SP, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5912-3409","authenticated-orcid":false,"given":"Od\u00edlia","family":"Queir\u00f3s","sequence":"additional","affiliation":[{"name":"UNIPRO\u2014Oral Pathology and Rehabilitation Research Unit, University Institute of Health Sciences, CESPU, CRL, 4585-116 Gandra, Portugal"}]},{"given":"Young H.","family":"Ko","sequence":"additional","affiliation":[{"name":"KoDiscovery, LLC, Institute of Marine and Environmental Technology (IMET) Center, 701 East Pratt Street, Baltimore, MD 21202, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1198-4776","authenticated-orcid":false,"given":"Barbara","family":"Kofler","sequence":"additional","affiliation":[{"name":"Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, University Hospital of the Paracelsus Medical University, 5020 Salzburg, Austria"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0143-9758","authenticated-orcid":false,"given":"Margarida","family":"Casal","sequence":"additional","affiliation":[{"name":"Center of Molecular and Environmental Biology (CBMA), University of Minho, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1770-4544","authenticated-orcid":false,"given":"F\u00e1tima","family":"Baltazar","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, Braga\/Guimar\u00e3es, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1038\/s41375-022-01613-1","article-title":"The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic\/Dendritic Neoplasms","volume":"36","author":"Khoury","year":"2022","journal-title":"Leukemia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1182\/blood-2016-03-643544","article-title":"The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia","volume":"127","author":"Arber","year":"2016","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1002\/ajh.25162","article-title":"Very poor long-term survival in past and more recent studies for relapsed AML patients: The ECOG-ACRIN experience","volume":"93","author":"Ganzel","year":"2018","journal-title":"Am. J. Hematol."},{"key":"ref_4","unstructured":"(2023, August 05). Cancer.Net. Leukemia-Acute Myeloid-AML. Available online: https:\/\/www.cancer.net\/cancer-types\/leukemia-acute-myeloid-aml\/statistics%2C%202023."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1182\/blood-2016-08-733196","article-title":"Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel","volume":"129","author":"Estey","year":"2017","journal-title":"Blood"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"8817","DOI":"10.2147\/CMAR.S177894","article-title":"Midostaurin In Acute Myeloid Leukemia: An Evidence-Based Review And Patient Selection","volume":"11","author":"Abbas","year":"2019","journal-title":"Cancer Manag. Res."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Wouters, B.J. (2021). Targeting IDH1 and IDH2 Mutations in Acute Myeloid Leukemia: Emerging Options and Pending Questions. HemaSphere, 5.","DOI":"10.1097\/HS9.0000000000000583"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.htct.2018.09.001","article-title":"Targeted therapy with a selective BCL-2 inhibitor in older patients with acute myeloid leukemia","volume":"41","author":"Campos","year":"2019","journal-title":"Hematol. Transfus. Cell Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1007\/s11864-020-00765-5","article-title":"Treatment of Relapsed Acute Myeloid Leukemia","volume":"21","author":"Thol","year":"2020","journal-title":"Curr. Treat. Options Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/nature22993","article-title":"Tracing the origins of relapse in acute myeloid leukaemia to stem cells","volume":"547","author":"Shlush","year":"2017","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.2147\/OTT.S191621","article-title":"Mechanisms of drug resistance in acute myeloid leukemia","volume":"12","author":"Zhang","year":"2019","journal-title":"OncoTargets Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1158\/2159-8290.CD-21-1059","article-title":"Hallmarks of Cancer: New Dimensions","volume":"12","author":"Hanahan","year":"2022","journal-title":"Cancer Discov."},{"key":"ref_13","unstructured":"Jain, B., and Pandey, S. (2022). Understanding Cancer, Academic Press."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3317","DOI":"10.1158\/0008-5472.CAN-14-0772-T","article-title":"IDH1 Mutations Alter Citric Acid Cycle Metabolism and Increase Dependence on Oxidative Mitochondrial Metabolism","volume":"74","author":"Grassian","year":"2016","journal-title":"Cancer Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1038\/nature24294","article-title":"BCAT1 restricts \u03b1KG levels in AML stem cells leading to IDHmut-like DNA hypermethylation","volume":"551","author":"Raffel","year":"2017","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2326","DOI":"10.1038\/leu.2017.81","article-title":"High mTORC1 activity drives glycolysis addiction and sensitivity to G6PD inhibition in acute myeloid leukemia cells","volume":"31","author":"Poulain","year":"2017","journal-title":"Leukemia"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1182\/blood-2014-02-554204","article-title":"A distinct glucose metabolism signature of acute myeloid leukemia with prognostic value","volume":"124","author":"Chen","year":"2014","journal-title":"Blood"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1126\/science.123.3191.309","article-title":"On the Origin of Cancer Cells","volume":"123","author":"Warburg","year":"1956","journal-title":"Science"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5","DOI":"10.3389\/fonc.2020.00005","article-title":"Metabolic Symbiosis in Chemoresistance: Refocusing the Role of Aerobic Glycolysis","volume":"10","author":"Ma","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.leukres.2007.04.014","article-title":"Glycolytic metabolism confers resistance to combined all-trans retinoic acid and arsenic trioxide-induced apoptosis in HL60\u03c10 cells","volume":"32","author":"Herst","year":"2008","journal-title":"Leuk. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1189\/jlb.0710417","article-title":"The level of glycolytic metabolism in acute myeloid leukemia blasts at diagnosis is prognostic for clinical outcome","volume":"89","author":"Herst","year":"2011","journal-title":"J. Leukoc. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"334","DOI":"10.3892\/ol.2016.4600","article-title":"Resistance to chemotherapy is associated with altered glucose metabolism in acute myeloid leukemia","volume":"12","author":"Song","year":"2016","journal-title":"Oncol. Lett."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.jmoldx.2016.10.002","article-title":"Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer","volume":"19","author":"Li","year":"2017","journal-title":"J. Mol. Diagn."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1016\/j.gim.2022.01.001","article-title":"Standards for the classification of pathogenicity of somatic variants in cancer (oncogenicity): Joint recommendations of Clinical Genome Resource (ClinGen), Cancer Genomics Consortium (CGC), and Variant Interpretation for Cancer Consortium (VICC)","volume":"24","author":"Horak","year":"2022","journal-title":"Genet. Med."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Lindstr\u00f6m, H.J.G., and Friedman, R. (2020). Inferring time-dependent population growth rates in cell cultures undergoing adaptation. BMC Bioinform., 21.","DOI":"10.1186\/s12859-020-03887-7"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Pereira-Nunes, A., Ferreira, H., Abreu, S., Guedes, M., Neves, N.M., Baltazar, F., and Granja, S. (2023). Combination Therapy with CD147-Targeted Nanopartic.pdf. Adv. Biol., 7.","DOI":"10.1002\/adbi.202300080"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1038\/s41568-020-00315-z","article-title":"Advances in germline predisposition to acute leukaemias and myeloid neoplasms","volume":"21","author":"Klco","year":"2021","journal-title":"Nat. Rev. Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"a034975","DOI":"10.1101\/cshperspect.a034975","article-title":"The Role of Somatic Mutations in Acute Myeloid Leukemia Pathogenesis","volume":"11","author":"Kishtagari","year":"2021","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_29","unstructured":"(2023, November 29). KEGG PATHWAY: Acute Myeloid Leukemia-Homo Sapiens (Human). Available online: https:\/\/www.genome.jp\/kegg-bin\/show_pathway?hsa05221."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1182\/bloodadvances.2021004292","article-title":"Prognostic impact of CEBPA bZIP domain mutation in acute myeloid leukemia","volume":"6","author":"Wakita","year":"2022","journal-title":"Blood Adv."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1016\/j.bbmt.2018.11.031","article-title":"FLT3-ITD and CEBPA Mutations Predict Prognosis in Acute Myelogenous Leukemia Irrespective of Hematopoietic Stem Cell Transplantation","volume":"25","author":"Wang","year":"2019","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1038\/ng.3400","article-title":"The genomic landscape of juvenile myelomonocytic leukemia","volume":"47","author":"Stieglitz","year":"2015","journal-title":"Nat. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1016\/j.ccell.2021.06.004","article-title":"Stepwise evolution of therapy resistance in AML","volume":"39","author":"Gui","year":"2021","journal-title":"Cancer Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.1158\/0008-5472.CAN-15-1015","article-title":"Genomic Profiling of Pediatric Acute Myeloid Leukemia Reveals a Changing Mutational Landscape from Disease Diagnosis to Relapse","volume":"76","author":"Farrar","year":"2016","journal-title":"Cancer Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"807266","DOI":"10.3389\/fonc.2022.807266","article-title":"Exploring the Metabolic Landscape of AML: From Haematopoietic Stem Cells to Myeloblasts and Leukaemic Stem Cells","volume":"12","author":"Mesbahi","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1038\/s41375-022-01541-0","article-title":"RAS activation induces synthetic lethality of MEK inhibition with mitochondrial oxidative metabolism in acute myeloid leukemia","volume":"36","author":"Decroocq","year":"2022","journal-title":"Leukemia"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1158\/2159-8290.CD-22-0411","article-title":"C\/EBP\u03b1 Confers Dependence to Fatty Acid Anabolic Pathways and Vulnerability to Lipid Oxidative Stress\u2013Induced Ferroptosis in FLT3-Mutant Leukemia","volume":"13","author":"Sabatier","year":"2023","journal-title":"Cancer Discov."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Ediriweera, M.K., and Jayasena, S. (2023). The Role of Reprogrammed Glucose Metabolism in Cancer. Metabolites, 13.","DOI":"10.3390\/metabo13030345"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Kreitz, J., Sch\u00f6nfeld, C., Seibert, M., Stolp, V., Alshamleh, I., Oellerich, T., Steffen, B., Schwalbe, H., Schn\u00fctgen, F., and Kurrle, N. (2019). Metabolic Plasticity of Acute Myeloid Leukemia. Cells, 8.","DOI":"10.3390\/cells8080805"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"155","DOI":"10.3389\/fonc.2020.00155","article-title":"Fatty Acid Metabolism, Bone Marrow Adipocytes, and AML","volume":"10","author":"Tabe","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1158\/2159-8290.CD-16-0441","article-title":"Chemotherapy-Resistant Human Acute Myeloid Leukemia Cells Are Not Enriched for Leukemic Stem Cells but Require Oxidative Metabolism","volume":"7","author":"Farge","year":"2017","journal-title":"Cancer Discov."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1007\/s10863-016-9670-z","article-title":"The anticancer agent 3-bromopyruvate: A simple but powerful molecule taken from the lab to the bedside","volume":"48","author":"Baltazar","year":"2016","journal-title":"J. Bioenerg. Biomembr."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/j.bbabio.2009.03.003","article-title":"Role of mitochondria-associated hexokinase II in cancer cell death induced by 3-bromopyruvate","volume":"1787","author":"Chen","year":"2009","journal-title":"Biochim. Biophys. Acta Bioenerg."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3892\/etm.2022.11447","article-title":"3-Bromopyruvic acid regulates glucose metabolism by targeting the c-Myc\/TXNIP axis and induces mitochondria-mediated apoptosis in TNBC cells","volume":"24","author":"Li","year":"2022","journal-title":"Exp. Ther. Med."},{"key":"ref_45","first-page":"2233","article-title":"3-Bromopyruvic Acid Inhibits Tricarboxylic Acid Cycle and Glutaminolysis in HepG2 Cells","volume":"36","year":"2016","journal-title":"Anticancer Res."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Garc\u00eda Rubi\u00f1o, M.E., Carrillo, E., Ruiz Alcal\u00e1, G., Dom\u00ednguez-Mart\u00edn, A., Marchal, J.A., and Boulaiz, H. (2019). Phenformin as an Anticancer Agent: Challenges and Prospects. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20133316"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3767","DOI":"10.1158\/1078-0432.CCR-18-0177","article-title":"Phenformin-Induced Mitochondrial Dysfunction Sensitizes Hepatocellular Carcinoma for Dual Inhibition of mTOR","volume":"24","author":"Veiga","year":"2018","journal-title":"Clin. Cancer Res."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/16\/4\/442\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:18:21Z","timestamp":1760105901000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/16\/4\/442"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,22]]},"references-count":47,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["pharmaceutics16040442"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics16040442","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,22]]}}}