{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T20:58:41Z","timestamp":1793048321074,"version":"4.5.0"},"reference-count":17,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T00:00:00Z","timestamp":1711324800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T00:00:00Z","timestamp":1711324800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The PI3K-AKT-mTOR pathway lies at the confluence of signaling pathways in which various components are subjected to activating genetic alterations in acute myeloid leukemia (AML), thus contributing to oncogenesis. Three\n                    <jats:italic>AKT<\/jats:italic>\n                    isoforms exist in humans. However, whether one isoform predominates in AML remains unknown. This study reveals that\n                    <jats:italic>AKT3<\/jats:italic>\n                    behaves very distinctly than\n                    <jats:italic>AKT1<\/jats:italic>\n                    or\n                    <jats:italic>AKT2<\/jats:italic>\n                    in both normal myeloid differentiation and AML. During normal differentiation,\n                    <jats:italic>AKT3<\/jats:italic>\n                    is preferentially expressed in hematopoietic stem cells whilst\n                    <jats:italic>AKT1<\/jats:italic>\n                    becomes preferentially expressed as cells differentiate into granulocytes or monocytes.\n                    <jats:italic>AKT2<\/jats:italic>\n                    expression remains unchanged. In AML,\n                    <jats:italic>AKT3<\/jats:italic>\n                    expression varies widely among patient samples and is counterintuitively high in mature\/monocytic leukemia. Furthermore, a low level of\n                    <jats:italic>AKT3<\/jats:italic>\n                    expression is strongly correlated to genetic alterations associated with a better outcome (\n                    <jats:italic>NPM1<\/jats:italic>\n                    mutations and\n                    <jats:italic>RUNX1<\/jats:italic>\n                    -\n                    <jats:italic>RUNX1T1<\/jats:italic>\n                    translocation), while a high level is correlated to alterations associated to a bad outcome (\n                    <jats:italic>RUNX1<\/jats:italic>\n                    mutations; and\n                    <jats:italic>SRSF2<\/jats:italic>\n                    ,\n                    <jats:italic>U2AF1<\/jats:italic>\n                    ,\n                    <jats:italic>SF3B1<\/jats:italic>\n                    ,\n                    <jats:italic>ASXL1<\/jats:italic>\n                    and\n                    <jats:italic>BCOR<\/jats:italic>\n                    mutations occurring frequently in MDS and MPN). Consistently, a high\n                    <jats:italic>AKT3<\/jats:italic>\n                    expression level appears as a very strong predictor of poor survival. Curiously, although modestly varying among AML samples, a high\n                    <jats:italic>AKT1<\/jats:italic>\n                    expression shows in contrast as a strong predictor of a better patient outcome. These data suggest that\n                    <jats:italic>AKT3<\/jats:italic>\n                    and\n                    <jats:italic>AKT1<\/jats:italic>\n                    expressions have strong, yet opposite, prognostic values.\n                  <\/jats:p>","DOI":"10.1038\/s41598-024-57578-x","type":"journal-article","created":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T17:40:27Z","timestamp":1711388427000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Differential prognostic values of the three AKT isoforms in acute myeloid leukemia"],"prefix":"10.1038","volume":"14","author":[{"given":"Eulalie","family":"Corre","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9cile","family":"Soum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romain","family":"Pfeifer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chlo\u00e9","family":"Bessi\u00e8re","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Dailhau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Marb\u0153uf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabienne","family":"Meggetto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Touriol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"R\u00e9cher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Bousquet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"Pyronnet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,25]]},"reference":[{"issue":"4","key":"57578_CR1","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1182\/blood-2016-08-733196","volume":"129","author":"H D\u00f6hner","year":"2017","unstructured":"D\u00f6hner, H. et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 129(4), 424\u2013447 (2017).","journal-title":"Blood."},{"issue":"12","key":"57578_CR2","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.1182\/blood.2022016867","volume":"140","author":"H D\u00f6hner","year":"2022","unstructured":"D\u00f6hner, H. et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood. 140(12), 1345\u20131377 (2022).","journal-title":"Blood."},{"issue":"5","key":"57578_CR3","doi-asserted-by":"publisher","first-page":"E964","DOI":"10.1152\/ajpendo.00239.2003","volume":"285","author":"J Faridi","year":"2003","unstructured":"Faridi, J., Fawcett, J., Wang, L. & Roth, R. A. Akt promotes increased mammalian cell size by stimulating protein synthesis and inhibiting protein degradation. Am. J. Physiol. Endocrinol. Metab. 285(5), E964\u2013E972 (2003).","journal-title":"Am. J. 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All other authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"7070"}}