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Characterization of Asciminib-Resistant Philadelphia Chromosome-Positive Cells.
Okabe, Seiichi; Moriyama, Mitsuru; Gotoh, Akihiko.
  • Okabe S; Department of Hematology, Tokyo Medical University, Tokyo, Japan.
  • Moriyama M; Department of Hematology, Tokyo Medical University, Tokyo, Japan.
  • Gotoh A; Department of Hematology, Tokyo Medical University, Tokyo, Japan.
World J Oncol ; 15(2): 319-324, 2024 Apr.
Article en En | MEDLINE | ID: mdl-38545482
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 BCRABL1 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.
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