Abstract
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.
Keywords:
Asciminib; Chronic myeloid leukemia; Omacetaxine; Philadelphia-positive cell; Ponatinib.
Copyright 2024, Okabe et al.
Grants and funding
The Japanese Ministry of Education, Culture, Sports, Science and Technology provided financial support for this study (20K07644). AG received research funding from Eisai Co., Ltd., Ono Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Nippon Shinyaku Co., Ltd., Chugai Pharmaceutical Co., Ltd., MSD K.K., Otsuka Pharmaceutical Co., Ltd., Sumitomo Pharma Co., Ltd., Nippon Shinyaku Co., Ltd., Bayer Yakuhin, Ltd., Daiichi Sankyo Co., Ltd., and Nihon Pharmaceutical Co., Ltd. AG received honoraria from Novartis Pharma K.K., Alexion Pharmaceuticals, Inc., Eisai Co., Ltd., Ono Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Nippon Shinyaku Co., Ltd., Chugai Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Sumitomo Pharma Co., Ltd., Daiichi Sankyo Co., Ltd., Nihon Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., Janssen Pharmaceutical K.K., Pfizer Japan Inc., and Sanofi K.K. AG received consulting fees from PharmaEssentia Japan K.K., Chugai Pharmaceutical Co., Ltd., and Alexion Pharmaceuticals, Inc. In addition, AG participated in the data safety monitoring board or advisory board of PharmaEssentia Japan K.K., Chugai Pharmaceutical Co., Ltd., and Alexion Pharmaceuticals, Inc. SO and MM report no conflict of interest.