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Contributions of MET activation to BCR-ABL1 tyrosine kinase inhibitor resistance in chronic myeloid leukemia cells
| Content Provider | Semantic Scholar |
|---|---|
| Author | Tsubaki, Masanobu Takeda, Tomoya Kino, Toshiki Sakai, Kazuko Itoh, Tatsuki Imano, Motohiro Nakayama, Takehisa Nishio, Kazuto Satou, Takao Nishida, Shozo |
| Copyright Year | 2017 |
| Abstract | 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. |
| Starting Page | 38717 |
| Ending Page | 38730 |
| Page Count | 14 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.oncotarget.com/index.php?journal=oncotarget&op=download&page=article&path%5B%5D=16314&path%5B%5D=58752 |
| PubMed reference number | 28418880v1 |
| Alternate Webpage(s) | https://doi.org/10.18632/oncotarget.16314 |
| DOI | 10.18632/oncotarget.16314 |
| Journal | Oncotarget |
| Volume Number | 8 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | B-Cell Receptor Complex BCR gene BCR protein, human Mutation Myeloid Leukemia Myeloid Leukemia, Chronic Nucleic Acid Hybridization Protein Tyrosine Kinase Protein-tyrosine kinase inhibitor Proto-Oncogene Proteins c-akt Tyrosine-Protein Kinase ABL1, human comparative genomic analysis imatinib |
| Content Type | Text |
| Resource Type | Article |
