{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T16:19:05Z","timestamp":1787588345319,"version":"build-2736575974"},"reference-count":81,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,8]],"date-time":"2023-01-08T00:00:00Z","timestamp":1673136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"AIRC","award":["10005"],"award-info":[{"award-number":["10005"]}]},{"name":"AIRC","award":["IG21408"],"award-info":[{"award-number":["IG21408"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hypoxia is a critical condition that governs survival, self-renewal, quiescence, metabolic shift and refractoriness to leukemic stem cell (LSC) therapy. The present study aims to investigate the hypoxia-driven regulation of the mammalian Target of the Rapamycin-2 (mTORC2) complex to unravel it as a novel potential target in chronic myeloid leukemia (CML) therapeutic strategies. After inducing hypoxia in a CML cell line model, we investigated the activities of mTORC1 and mTORC2. Surprisingly, we detected a significant activation of mTORC2 at the expense of mTORC1, accompanied by the nuclear localization of the main substrate phospho-Akt (Ser473). Moreover, the Gene Ontology analysis of CML patients\u2019 CD34+ cells showed enrichment in the mTORC2 signature, further strengthening our data. The deregulation of mTOR complexes highlights how hypoxia could be crucial in CML development. In conclusion, we propose a mechanism by which CML cells residing under a low-oxygen tension, i.e., in the leukemia quiescent LSCs, singularly regulate the mTORC2 and its downstream effectors.<\/jats:p>","DOI":"10.3390\/ijms24021234","type":"journal-article","created":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T02:09:39Z","timestamp":1673230179000},"page":"1234","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["mTORC2 Is Activated under Hypoxia and Could Support Chronic Myeloid Leukemia Stem Cells"],"prefix":"10.3390","volume":"24","author":[{"given":"Cristina","family":"Panuzzo","sequence":"first","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Turin, 10043 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucrezia","family":"Pironi","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Turin, 10043 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7153-2248","authenticated-orcid":false,"given":"Alessandro","family":"Maglione","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Turin, 10043 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8805-959X","authenticated-orcid":false,"given":"Simone","family":"Rocco","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Turin, 10043 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1454-0713","authenticated-orcid":false,"given":"Serena","family":"Stanga","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Rita Levi Montalcini, Neuroscience Institute Cavalieri Ottolenghi, University of Turin, 10043 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9787-4836","authenticated-orcid":false,"given":"Chiara","family":"Riganti","sequence":"additional","affiliation":[{"name":"Department of Oncology, University of Turin, 10043 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3612-3953","authenticated-orcid":false,"given":"Joanna","family":"Kopecka","sequence":"additional","affiliation":[{"name":"Department of Oncology, University of Turin, 10043 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6234-8369","authenticated-orcid":false,"given":"Muhammad Shahzad","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Turin, 10043 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4686-0068","authenticated-orcid":false,"given":"Barbara","family":"Pergolizzi","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Turin, 10043 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3170-2817","authenticated-orcid":false,"given":"Enrico","family":"Bracco","sequence":"additional","affiliation":[{"name":"Department of Oncology, University of Turin, 10043 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6346-4791","authenticated-orcid":false,"given":"Daniela","family":"Cilloni","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Turin, 10043 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Arnouk, H., and Abdul Rasool Hassan, B. 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