Radotinib induces high cytotoxicity in c-KIT positive acute myeloid leukemia cells
- Authors
- Heo, Sook-Kyoung; Noh, Eui-Kyu; Kim, Jeong Yi; Jo, Jae-Cheol; Choi, Yunsuk; Koh, Sujin; Baek, Jin Ho; Min, Young Joo; Kim, Hawk
- Issue Date
- 5-Jun-2017
- Publisher
- ELSEVIER SCIENCE BV
- Keywords
- Radotinib; Acute myeloid leukemia; c-KIT; CD117; Cytotoxicity; Anti-leukemic activity
- Citation
- EUROPEAN JOURNAL OF PHARMACOLOGY, v.804, pp.52 - 56
- Journal Title
- EUROPEAN JOURNAL OF PHARMACOLOGY
- Volume
- 804
- Start Page
- 52
- End Page
- 56
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/6004
- DOI
- 10.1016/j.ejphar.2017.03.040
- ISSN
- 0014-2999
- Abstract
- Previously, we reported that radotinib, a BCR-ABL1 tyrosine kinase inhibitor, induced cytotoxicity in acute myeloid leukemia (AML) cells. However, the effects of radotinib in the subpopulation of c-KIT-positive AML cells were unclear. We observed that low-concentration radotinib had more potent cytotoxicity in c-KIT-positive cells than c-KIT-negative cells from AML patients. To address this issue, cell lines with high c-KIT expression, HEL92.1.7, and moderate c-KIT expression, H209, were selected. HEL92.1.7 cells were grouped into intermediate and high c-HIT expression populations. The cytotoxicity of radotinib against the HEL92.1.7 cell population with intermediate c-HIT expression was not different from that of the population with high c-KIT expression. When H209 cells were grouped into c-KIT expression-negative and c-HIT expression-positive populations, radotinib induced cytotoxicity in the c-KIT-positive population, but not the c-KIT-negative population. Thus, radotinib induces cytotoxicity in c-KIT-positive cells, regardless of the c-KIT expression intensity. Therefore, radotinib induces significant cytotoxicity in c-KIT-positive AML cells, suggesting that radotinib is a potential target agent for the treatment of c-KIT-positive malignancies including AML.
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