{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T02:11:43Z","timestamp":1783476703674,"version":"3.55.0"},"reference-count":41,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T00:00:00Z","timestamp":1754611200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["21nk0101564"],"award-info":[{"award-number":["21nk0101564"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FEBS Open Bio"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:p>\n                    Acute myeloid leukemia (AML) is a bone marrow malignancy characterized by arrested early\u2010stage hematopoietic precursor development. Differentiation therapy, which induces terminal differentiation of immature leukemic cells, is less toxic than standard intensive chemotherapy and a promising treatment strategy for AML. Despite the success of all\u2010trans retinoic acid and arsenic trioxide in treating acute promyelocytic leukemia (APL), effective differentiation therapy for non\u2010APL AML has not been established. We previously demonstrated that dihydropyrimidinase\u2010like 2A (DPYSL2A) is crucial for the monocytic differentiation of AML cells. In this study, analysis using the Comparative Toxicogenomics Database identified statins, which are well\u2010known cholesterol\u2010lowering drugs, as potential compounds that upregulate\n                    <jats:italic>DPYSL2A<\/jats:italic>\n                    expression in a Kr\u00fcppel\u2010like factor 4 (KLF4)\u2010dependent manner. Most of the tested statins promoted the monocytic differentiation of non\u2010APL AML cells, leading to rapid apoptosis. The statin\u2010induced effects were reversed by mevalonate (MVA) supplementation, indicating dependence on MVA pathway inhibition. Furthermore, the inhibition of protein farnesylation, a downstream process of the MVA pathway, mimicked the statin\u2010induced effects, suggesting that farnesylation suppression is essential for statin\u2010induced\n                    <jats:italic>KLF4\/DPYSL2A<\/jats:italic>\n                    expression and monocytic differentiation. These findings may help develop more effective differentiation therapies for patients with non\u2010APL AML.\n                  <\/jats:p>","DOI":"10.1002\/2211-5463.70104","type":"journal-article","created":{"date-parts":[[2025,8,9]],"date-time":"2025-08-09T05:43:41Z","timestamp":1754718221000},"page":"2021-2030","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Statins induce monocytic differentiation in acute myeloid leukemia cells through the\n                    <scp>KLF4<\/scp>\n                    \/\n                    <scp>DPYSL2A<\/scp>\n                    axis"],"prefix":"10.1002","volume":"15","author":[{"given":"Mina","family":"Noura","sequence":"first","affiliation":[{"name":"Division of Cellular and Genetic Sciences, Department of Integrated Health Sciences Nagoya University Graduate School of Medicine  Japan"},{"name":"Human Health Sciences, Graduate School of Medicine Kyoto University  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