{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:53:05Z","timestamp":1787313185319,"version":"build-2736575974"},"reference-count":59,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2014NextGenerationEU","award":["PE_00000015\u2014CUP: C13C22000660001"],"award-info":[{"award-number":["PE_00000015\u2014CUP: C13C22000660001"]}]},{"name":"CIB\u2014Consorzio Interuniversitario Biotecnologie"},{"name":"AGING Project, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale Novara, Italy"},{"name":"AIRC","award":["IG-25702"],"award-info":[{"award-number":["IG-25702"]}]},{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"crossref","award":["RF-2021-12373598"],"award-info":[{"award-number":["RF-2021-12373598"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Italian Ministry of University and Research","award":["PRIN-2022 9CJ27R"],"award-info":[{"award-number":["PRIN-2022 9CJ27R"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Acute myeloid leukemia (AML) is a heterogeneous disease with an unmet need for novel therapeutic drugs. Previous studies have reported the upregulation of diacylglycerol kinases (DGKs) in AML. This study investigated the effects of ritanserin, a DGK\u03b1-specific inhibitor, and DGK\u03b6-IN4 or BAY 2965501, DGK\u03b6-selective inhibitors, on a panel of AML cell lines. Ritanserin induced apoptotic cell death across all tested models, whereas DGK\u03b6 inhibitors triggered both apoptosis and necrosis to variable extents, with HL-60 cells being the most responsive to both compounds. Drug sensitivity did not correlate with DGK\u03b1 or DGK\u03b6 expression levels, indicating that additional factors may influence cellular susceptibility. THP-1 proteomic profiling revealed that ritanserin broadly downregulated proteins involved in antigen presentation, cell cycle and metabolism, while BAY 2965501 affected a smaller and distinct but functionally similar protein subset, implying different mechanisms of action. Gene silencing confirmed AML cell line-specific dependence on DGK isoforms: HEL cells were sensitive to DGK\u03b1 knockdown, HL-60 to DGK\u03b6 silencing, whereas K562 and THP-1 were resistant to both. These findings indicate that DGKs targeting can effectively reduce AML cell viability. However, AML heterogeneity and the limited selectivity of current inhibitors underscore the need for predictive biomarkers and combinatorial strategies to translate DGK inhibition into effective therapy.<\/jats:p>","DOI":"10.3390\/cells14211721","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T13:47:58Z","timestamp":1762177678000},"page":"1721","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Acute Myeloid Leukemia: A Key Role of DGK\u03b1 and DGK\u03b6 in Cell Viability"],"prefix":"10.3390","volume":"14","author":[{"given":"Elisa","family":"Gorla","sequence":"first","affiliation":[{"name":"Center for Translational Research on Autoimmune and Allergic Diseases, University of Eastern Piedmont, 28100 Novara, Italy"},{"name":"Department of Translational Medicine, University of Eastern Piedmont, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco Cristiano","family":"Cartella","sequence":"additional","affiliation":[{"name":"Center for Translational Research on Autoimmune and Allergic Diseases, University of Eastern Piedmont, 28100 Novara, Italy"},{"name":"Department of Translational Medicine, University of Eastern Piedmont, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edoardo","family":"Borghetti","sequence":"additional","affiliation":[{"name":"Center for Translational Research on Autoimmune and Allergic Diseases, University of Eastern Piedmont, 28100 Novara, Italy"},{"name":"Department of Translational Medicine, University of Eastern Piedmont, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ginevra","family":"Lovati","sequence":"additional","affiliation":[{"name":"Center for Translational Research on Autoimmune and Allergic Diseases, University of Eastern Piedmont, 28100 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University of Eastern Piedmont, 28100 Novara, Italy"},{"name":"Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center (MBC Guido Tarone), University of Turin, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"De Giorgis","sequence":"additional","affiliation":[{"name":"Center for Translational Research on Autoimmune and Allergic Diseases, University of Eastern Piedmont, 28100 Novara, Italy"},{"name":"Department of Translational Medicine, University of Eastern Piedmont, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4123-1705","authenticated-orcid":false,"given":"Davide","family":"Cor\u00e0","sequence":"additional","affiliation":[{"name":"Center for Translational Research on Autoimmune and Allergic Diseases, University of Eastern Piedmont, 28100 Novara, Italy"},{"name":"Department of Translational Medicine, University of Eastern 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