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<p>Current therapeutic options for myelodysplastic neoplasms (MDS)-associated thrombocytopenia are limited. 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.</p>

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Unraveling the impact of crizotinib to promote megakaryopoiesis for alleviating thrombocytopenia in myelodysplastic neoplasms

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月14日

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  • Hiroki Kobayashi,
  • Yuta Komizo,
  • Nanami Watanabe,
  • Yu Miyata,
  • Yoshiya Ohnuma,
  • Yasushige Kamimura-Aoyagi,
  • Kanako Yuki,
  • Yoshihiro Hayashi,
  • Minoru Yoshida,
  • Yuka Harada,
  • Hironori Harada

摘要

Current therapeutic options for myelodysplastic neoplasms (MDS)-associated thrombocytopenia are limited. 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.