Characterization of Asciminib-Resistant Philadelphia Chromosome-Positive Cells.

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.