World journal of oncology · 2024
Characterization of Asciminib-Resistant Philadelphia Chromosome-Positive Cells.
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Okabe Seiichi, Moriyama Mitsuru, Gotoh Akihiko
Аннотация
BACKGROUND: Asciminib is approved for treating patients with chronic-phase chronic myeloid leukemia who were previously treated with two or more tyrosine kinase inhibitors or those with T315I mutation. However, the mechanisms underlying asciminib resistance remain unclear.
METHODS: In this study, we established a new asciminib-resistant cell line. We examined BCR::ABL1 gene mutation analysis and the effects of conventional chronic myelogenous leukemia inhibitors.
RESULTS: Direct sequencing revealed Y139D and T315I mutations in asciminib-resistant cells. Ponatinib and omacetaxine were effective against asciminib-resistant cells.
CONCLUSIONS: Y139D and T315I mutations are extremely resistant to asciminib. Ponatinib and omacetaxine show potential for treating asciminib-resistant chronic myeloid leukemia.
METHODS: In this study, we established a new asciminib-resistant cell line. We examined BCR::ABL1 gene mutation analysis and the effects of conventional chronic myelogenous leukemia inhibitors.
RESULTS: Direct sequencing revealed Y139D and T315I mutations in asciminib-resistant cells. Ponatinib and omacetaxine were effective against asciminib-resistant cells.
CONCLUSIONS: Y139D and T315I mutations are extremely resistant to asciminib. Ponatinib and omacetaxine show potential for treating asciminib-resistant chronic myeloid leukemia.