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image of YM155 Restores the Effect of Imatinib in Imatinib-Resistant Chronic Myeloid Leukemia Cell Lines

Abstract

Introduction

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the Philadelphia chromosome. Imatinib is considered the standard therapy for CML due to its targeted action against the BCR::ABL1 tyrosine kinase. However, resistance to imatinib often emerges, particularly in the advanced stages of CML. One factor associated with imatinib resistance is the overexpression of survivin (baculoviral IAP repeat-containing 5, BIRC5). YM155 is an innovative survivin inhibitor that suppresses survivin expression and triggers apoptosis. Combination therapy is a strategy used to enhance the effectiveness of cancer treatment and overcome resistance.

Methods

Our study explored the in vitro anticancer effects of YM155 as monotherapy and as a combination therapy with imatinib on imatinib-sensitive (K-562) and imatinib-resistant (K562-r) BCR::ABL1+ CML cell lines. Results: Survivin inhibition significantly reduced proliferation in both K-562 and K562-r cells. Combination therapy with YM155 and imatinib produced a synergistic effect. In K562-r cells (imatinib IC = 6 µM), the combination reduced the IC by 6.2-fold. In K-562 cells, the IC decreased by 16.3-fold. Both monotherapy and combination therapy markedly increased apoptosis, with combination therapy inducing significantly greater apoptosis. The combination also downregulated survivin and BCR::ABL1 tyrosine kinase expression and significantly reduced BCR::ABL1 mRNA levels.

Conclusion

YM155 enhances imatinib’s efficacy against both sensitive and resistant CML cells, overcoming resistance through synergistic inhibition of proliferation, increased apoptosis, and suppression of survivin and BCR::ABL1 expression. These results support further investigation of YM155-Imatinib combination therapy as a potential strategy for resistant CML.

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2025-10-27
2025-12-24

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YM155 Restores the Effect of Imatinib in Imatinib-Resistant Chronic Myeloid Leukemia Cell Lines
Bentham Science Publishers ; https://doi.org/10.2174/0115680096402329251002224513
/content/journals/ccdt/10.2174/0115680096402329251002224513
/content/journals/ccdt/10.2174/0115680096402329251002224513
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  • Article Type:     Research Article
Keywords: survivin inhibitor ; YM155 ; BCR-ABL ; BIRC5 ; imatinib resistance ; imatinib ; surviving ; Chronic myelogenous leukemia

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