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Megakaryocyte maturation might be an innovative therapeutic strategy because its dysregulation profoundly contributes to MDS pathogenesis. Here, we identified crizotinib, a clinically approved anti-cancer drug for anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer, as a potent inducer of megakaryocyte maturation. We demonstrated that crizotinib effectively induced polyploidization to increase the platelet-producing capacity of megakaryocytes derived from an MDS murine model and MDS patients by targeting Aurora kinases rather than its canonical targets, ALK\/ROS1\/c-MET. Importantly, crizotinib administration substantially ameliorated thrombocytopenia in our preclinical model. Our findings underscore the remarkable potential of crizotinib for drug repurposing and offer a novel therapeutic strategy for MDS patients with thrombocytopenia facing health-related quality of life concerns.<\/jats:p>","DOI":"10.1038\/s41375-025-02729-w","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T08:14:20Z","timestamp":1755159260000},"page":"2789-2800","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Unraveling the impact of crizotinib to promote megakaryopoiesis for alleviating thrombocytopenia in myelodysplastic neoplasms"],"prefix":"10.1038","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3785-2317","authenticated-orcid":false,"given":"Hiroki","family":"Kobayashi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuta","family":"Komizo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nanami","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Miyata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiya","family":"Ohnuma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasushige","family":"Kamimura-Aoyagi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kanako","family":"Yuki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshihiro","family":"Hayashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4376-5674","authenticated-orcid":false,"given":"Minoru","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4550-3176","authenticated-orcid":false,"given":"Yuka","family":"Harada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9401-5470","authenticated-orcid":false,"given":"Hironori","family":"Harada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,8,14]]},"reference":[{"key":"2729_CR1","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1200\/JCO.2009.24.7999","volume":"28","author":"H Kantarjian","year":"2010","unstructured":"Kantarjian H, Fenaux P, Sekeres MA, Becker PS, Boruchov A, Bowen D, et al. 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Patent names: \u201cTherapeutic compounds for hematological disorders.\u201d Patent applicant: Tokyo University of Pharmacy and Life Sciences. Name of inventors: HK and HH. Patent number: Japanese Patent Application No. 2024-228529. Patent status: pending. Specific aspect of the manuscript covered in the patent application: The patent application covers the application of crizotinib to increase platelet counts in MDS patients. HK received a research grant from Nippon Shinyaku Co., Ltd. HH has received advisory board fees from Novartis. The other authors have no conflicts of interest to declare.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}