Targeting c-KIT (CD117) by dasatinib and radotinib promotes acute myeloid leukemia cell death
DC Field | Value | Language |
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dc.contributor.author | Heo, Sook-Kyoung | - |
dc.contributor.author | Noh, Eui-Kyu | - |
dc.contributor.author | Kim, Jeong Yi | - |
dc.contributor.author | Jeong, Yoo Kyung | - |
dc.contributor.author | Jo, Jae-Cheol | - |
dc.contributor.author | Choi, Yunsuk | - |
dc.contributor.author | Koh, SuJin | - |
dc.contributor.author | Baek, Jin Ho | - |
dc.contributor.author | Min, Young Joo | - |
dc.contributor.author | Kim, Hawk | - |
dc.date.available | 2020-02-27T16:42:48Z | - |
dc.date.created | 2020-02-06 | - |
dc.date.issued | 2017-11 | - |
dc.identifier.issn | 2045-2322 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/5482 | - |
dc.description.abstract | Dasatinib and radotinib are oral BCR-ABL tyrosine kinase inhibitors that were developed as drugs for the treatment of chronic myeloid leukemia. We report here that the c-KIT (CD117) targeting with dasatinib and radotinib promotes acute myeloid leukemia (AML) cell death, and c-KIT endocytosis is essential for triggering c-KIT-positive AML cell death by dasatinib and radotinib during the early stages. In addition, dasatinib and radotinib reduce heat shock protein 90 beta (HSP90 beta) expression and release Apaf-1 in c-KIT-positive AML cells. Finally, this activates a caspase-dependent apoptotic pathway in c-KIT-positive AML cells. Moreover, the inhibition of c-KIT endocytosis by dynamin inhibitor (DY) reversed cell viability and c-KIT expression by dasatinib and radotinib. HSP90 beta expression was recovered by DY in c-KIT-positive AML cells as well. Furthermore, the effect of radotinib on c-KIT and HSP90 beta showed the same pattern in a xenograft animal model using HEL92.1.7 cells. Therefore, dasatinib and radotinib promote AML cell death by targeting c-KIT. Taken together, these results indicate that dasatinib and radotinib treatment have a potential role in anti-leukemic therapy on c-KIT-positive AML cells. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | NATURE PUBLISHING GROUP | - |
dc.relation.isPartOf | SCIENTIFIC REPORTS | - |
dc.title | Targeting c-KIT (CD117) by dasatinib and radotinib promotes acute myeloid leukemia cell death | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000414917800018 | - |
dc.identifier.doi | 10.1038/s41598-017-15492-5 | - |
dc.identifier.bibliographicCitation | SCIENTIFIC REPORTS, v.7 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.scopusid | 2-s2.0-85033575083 | - |
dc.citation.title | SCIENTIFIC REPORTS | - |
dc.citation.volume | 7 | - |
dc.contributor.affiliatedAuthor | Kim, Hawk | - |
dc.type.docType | Article | - |
dc.subject.keywordPlus | THERAPEUTIC TARGET | - |
dc.subject.keywordPlus | PHASE-I | - |
dc.subject.keywordPlus | HSP90 | - |
dc.subject.keywordPlus | INHIBITOR | - |
dc.subject.keywordPlus | KINASE | - |
dc.subject.keywordPlus | LINE | - |
dc.subject.keywordPlus | BORTEZOMIB | - |
dc.subject.keywordPlus | APOPTOSIS | - |
dc.subject.keywordPlus | PROLIFERATION | - |
dc.subject.keywordPlus | CHEMOTHERAPY | - |
dc.relation.journalResearchArea | Science & Technology - Other Topics | - |
dc.relation.journalWebOfScienceCategory | Multidisciplinary Sciences | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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