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

  • Leukemia. 2025 Aug 14. doi: 10.1038/s41375-025-02729-w.
Hiroki Kobayashi  1 ,  Yuta Komizo  2 ,  Nanami Watanabe  2 ,  Yu Miyata  2 ,  Yoshiya Ohnuma  2 ,  Yasushige Kamimura-Aoyagi  2 ,  Kanako Yuki  2 ,  Yoshihiro Hayashi  2  3 ,  Minoru Yoshida  4  5 ,  Yuka Harada  6 ,  Hironori Harada  2  7
Affiliations
  • 1. Laboratory of Oncology, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan. [email protected].
  • 2. Laboratory of Oncology, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
  • 3. Laboratory of Cancer Pathobiology and Therapeutics, Ritsumeikan University, Kusatsu, Japan.
  • 4. Chemical Genomics Research Group, RIKEN Center for Sustainable Resource Science, Wako, Japan.
  • 5. Drug Discovery Seeds Development Unit, RIKEN Center for Sustainable Resource Science, Wako, Japan.
  • 6. Department of Clinical Laboratory, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan.
  • 7. Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan.
PMID: 40813622 DOI: 10.1038/s41375-025-02729-w
Abstract

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.

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