2017年6月13日
Contributions of MET activation to BCR-ABL1 tyrosine kinase inhibitor resistance in chronic myeloid leukemia cells.
Oncotarget
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- 巻
- 8
- 号
- 24
- 開始ページ
- 38717
- 終了ページ
- 38730
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.18632/oncotarget.16314
- 出版者・発行元
- IMPACT JOURNALS LLC
Resistance to the breakpoint cluster region-abelson 1 (BCR-ABL1) tyrosine kinase inhibitor (TKI) imatinib poses a major problem when treating chronic myeloid leukemia (CML). Imatinib resistance often results from a secondary mutation in BCR-ABL1. However, in the absence of a mutation in BCR-ABL1, the basis of BCR-ABL1-independent resistance must be elucidated. To gain insight into the mechanisms of BCR-ABL1-independent imatinib resistance, we performed an array-based comparative genomic hybridization. We identified various resistance-related genes, and focused on MET. Treatment with a MET inhibitor resensitized K562/IR cells to BCR-ABL1 TKIs. Combined treatment of K562/IR cells with imatinib and a MET inhibitor suppressed extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK) activation, but did not affect AKT activation. Our findings implicate the MET/ERK and MET/JNK pathways in conferring resistance to imatinib, providing new insights into the mechanisms of BCR-ABL1 TKI resistance in CML.
- リンク情報
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- DOI
- https://doi.org/10.18632/oncotarget.16314
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/28418880
- PubMed Central
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5503566
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000403311900055&DestApp=WOS_CPL
- ID情報
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- DOI : 10.18632/oncotarget.16314
- eISSN : 1949-2553
- PubMed ID : 28418880
- PubMed Central 記事ID : PMC5503566
- Web of Science ID : WOS:000403311900055