Use of deferasirox, an iron chelator, to overcome imatinib resistance of chronic myeloid leukemia cells
- Authors
- Kim, Dae Sik; Na, Yoo Jin; Kang, Myoung Hee; Yoon, Soo-Young; Choi, Chul Won
- Issue Date
- 3월-2016
- Publisher
- KOREAN ASSOC INTERNAL MEDICINE
- Keywords
- Deferasirox; Iron chelator; Chronic myeloid leukemia; Imatinib; Resistance
- Citation
- KOREAN JOURNAL OF INTERNAL MEDICINE, v.31, no.2, pp.357 - 366
- Indexed
- SCIE
SCOPUS
KCI
- Journal Title
- KOREAN JOURNAL OF INTERNAL MEDICINE
- Volume
- 31
- Number
- 2
- Start Page
- 357
- End Page
- 366
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/89443
- DOI
- 10.3904/kjim.2015.024
- ISSN
- 1226-3303
- Abstract
- Background/Aims: The treatment of chronic myeloid leukemia (CML) has achieved impressive success since the development of the Bcr-Abl tyrosine kinase inhibitor, imatinib mesylate. Nevertheless, resistance to imatinib has been observed, and a substantial number of patients need alternative treatment strategies. Methods: We have evaluated the effects of deferasirox, an orally active iron chelator, and imatinib on K562 and KU812 human CML cell lines. Imatinib-resistant CML cell lines were created by exposing cells to gradually increasing concentrations of imatinib. Results: Co-treatment of cells with deferasirox and imatinib induced a synergistic dose-dependent inhibition of proliferation of both CML cell lines. Cell cycle analysis showed an accumulation of cells in the subG1 phase. Western blot analysis of apoptotic proteins showed that co-treatment with deferasirox and imatinib induced an increased expression of apoptotic proteins. These tendencies were clearly identified in imatinib-resistant CML cell lines. The results also showed that co-treatment with deferasirox and imatinib reduced the expression of Bcr-Abl, phosphorylated Bcr-Abl, nuclear factor-kappa B (NF-kappa B) and beta-catenin. Conclusions: We observed synergistic effects of deferasirox and imatinib on both imatinib-resistant and imatinib-sensitive cell lines. These effects were due to induction of apoptosis and cell cycle arrest by down-regulated expression of NF-kappa B and beta-catenin levels. Based on these results, we suggest that a combination treatment of deferasirox and imatinib could be considered as an alternative treatment option for imatinib-resistant CML.
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Collections - College of Medicine > Department of Medical Science > 1. Journal Articles
- Graduate School > Department of Biomedical Sciences > 1. Journal Articles
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