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December 8, 2025BloodOpen Access

FBXO3-mediated DUSP9 ubiquitination reprograms MAPK signaling to eradicate tyrosine kinase inhibitor-resistant CML stem cells

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Authors

XLXudong LiRXRongfeng XuYSYongping Song

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Overview

Experimental findings demonstrate how FBXO3 targeting improves outcomes in leukemic stem cells resistant to tyrosine kinase inhibitors.

Key Points

  • This research focuses on the role of FBXO3 in regulating leukemic stem cells in chronic myeloid leukemia resistant to treatment.
  • Utilized single-cell RNA sequencing to assess FBXO3 expression in CML patients and healthy individuals.
  • Interferred with FBXO3 using shRNA and sgRNA in CML cell lines, examining effects on cell growth and apoptosis.
  • Established various CML mouse models to validate FBXO3's role in leukemic stem cells.
  • Used mass spectrometry and co-IP to identify FBXO3 substrates like DUSP9 and confirm their ubiquitination.
  • Conducted RNA-sequencing to explore downstream signaling pathways influenced by FBXO3.
  • FBXO3 expression is higher in CML patients and affects growth and apoptosis of leukemic stem cells.
  • Knockdown of FBXO3 impairs growth and increases apoptosis in CML cells, reducing tumor volumes in vivo.
  • FBXO3 regulates DUSP9 through ubiquitination, affecting the MAPK pathway and apoptosis activation.
  • The FBXO3 inhibitor BC1215 enhances the effects of imatinib, targeting CML stem cells more effectively.

Cite This Study

Li et al. (2025) studied this question.

synapsesocial.com/papers/693624d74fa91c937236d0ddhttps://doi.org/10.1182/blood-2025-3754
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