{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:37:57Z","timestamp":1790656677424,"version":"4.1.0"},"reference-count":20,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2019,6,27]],"date-time":"2019-06-27T00:00:00Z","timestamp":1561593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Since many oncogenes, including BCR-ABL, may promote the acquisition and maintenance of the glycolytic phenotype, we tested whether treatment of BCR-ABL-driven human leukemia cells with imatinib, a selective BCR-ABL inhibitor, can modulate the expression of key glycolytic enzymes and mitochondrial complex subunits thus causing alterations of glucose metabolism. BCR-ABL-driven K562 and KCL-22 cells were incubated with increasing concentrations of imatinib to preliminarily test drug sensitivity. Then untreated and treated cells were analyzed for levels of BCR-ABL signaling mediators and key proteins of glycolytic cascade and oxidative phosphorylation. Effective inhibition of BCR-ABL caused a concomitant reduction of p-ERK1\/2, p-AKT, phosphorylated form of STAT3 (at Tyr705 and Ser727), c-Myc and cyclin D1 along with an increase of cleaved PARP and caspase 3 at 48 h after treatment. Furthermore, a strong reduction of the hexokinase II (HKII), phosphorylated form of PKM2 (at Tyr105 and Ser37) and lactate dehydrogenase A (LDH-A) was observed in response to imatinib along with a strong upregulation of mitochondrial complexes (OXPHOS). According to these findings, a significant reduction of glucose consumption and lactate secretion along with an increase of intracellular ATP levels was observed in response to imatinib. Our findings indicate that imatinib treatment of BCR-ABL-driven human leukemia cells reactivates mitochondrial oxidative phosphorylation thus allowing potential co-targeting of BCR-ABL and OXPHOS.<\/jats:p>","DOI":"10.3390\/ijms20133134","type":"journal-article","created":{"date-parts":[[2019,6,27]],"date-time":"2019-06-27T07:59:57Z","timestamp":1561622397000},"page":"3134","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Coordinate Modulation of Glycolytic Enzymes and OXPHOS by Imatinib in BCR-ABL Driven Chronic Myelogenous Leukemia Cells"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0430-5608","authenticated-orcid":false,"given":"Viviana","family":"De Rosa","sequence":"first","affiliation":[{"name":"Institute of Biostructures and Bioimaging, National Research Council, 80145 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcello","family":"Monti","sequence":"additional","affiliation":[{"name":"Department of Advanced Biomedical Sciences, University of Naples \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Terlizzi","sequence":"additional","affiliation":[{"name":"Department of Advanced Biomedical Sciences, University of Naples \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Fonti","sequence":"additional","affiliation":[{"name":"Institute of Biostructures and Bioimaging, National Research Council, 80145 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5466-1213","authenticated-orcid":false,"given":"Silvana","family":"Del Vecchio","sequence":"additional","affiliation":[{"name":"Department of Advanced Biomedical Sciences, University of Naples \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5132-3593","authenticated-orcid":false,"given":"Francesca","family":"Iommelli","sequence":"additional","affiliation":[{"name":"Institute of Biostructures and Bioimaging, National Research Council, 80145 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,6,27]]},"reference":[{"key":"ref_1","first-page":"1497","article-title":"A minute chromosome in human chronic granulocotic leukemia","volume":"132","author":"Nowell","year":"1960","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1038\/nrc1567","article-title":"Mechanisms of bcr-abl in the pathogenesis of chronic myelogenous leukaemia","volume":"5","author":"Ren","year":"2005","journal-title":"Nat. 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