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Updated: Apr 6, 2026
Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
Anti-leukemic activity of axitinib against cells harboring the BCR-ABL T315I point mutation
Seiichi Okabe1, Tetsuzo Tauchi2, Yuko Tanaka3
1Department of Hematology, Tokyo Medical University, 6-7-1 Nishi-shinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan. okabe@tokyo-med.ac.jp.
Abstract:
The BCR-ABL; breakpoint cluster region-Abelson point mutation T315I is resistant to ABL tyrosine kinase inhibitors. However, axitinib, a vascular endothelial growth factor receptor inhibitor, is effective against this mutation. In this study, we investigated axitinib activity against ponatinib-resistant cells and found that axitinib inhibited cellular growth and apoptosis in Ba/F3 T315I-mutant cells and T315I-mutant primary samples, but not in ponatinib-resistant Ba/F3 cells and primary samples. Thus, an alternative strategy may be required to improve the prognosis of Philadelphia-chromosome-positive leukemia patients harboring BCR-ABL point mutations.
Insights
Axitinib shows efficacy against the BCR-ABL T315I mutation in leukemia cells. However, it is ineffective against ponatinib-resistant cells, suggesting alternative strategies are needed for Philadelphia chromosome-positive leukemia.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- The T315I mutation in BCR-ABL confers resistance to ABL tyrosine kinase inhibitors.
- Axitinib, a VEGFR inhibitor, demonstrates activity against the T315I mutation.
Discussion:
- This study evaluated axitinib's efficacy in ponatinib-resistant cell lines and primary samples.
- Axitinib inhibited growth and induced apoptosis in T315I-mutant cells but not in ponatinib-resistant cells.
Key Insights:
- Axitinib is effective against BCR-ABL T315I mutations.
- Axitinib does not overcome resistance in ponatinib-resistant leukemia cells.
Outlook:
- Alternative therapeutic strategies are necessary for Philadelphia chromosome-positive leukemia patients with BCR-ABL point mutations.
- Further research is needed to identify novel treatments for resistant forms of leukemia.
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