Radotinib induces high cytotoxicity in c-KIT positive acute myeloid leukemia cells.
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-KIT expression populations. The cytotoxicity of radotinib against the HEL92.1.7 cell population with intermediate c-KIT 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-KIT 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.
Biomedical Research Center, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 682-060, Republic of Korea.
Sook-Kyoung
SK
Heo
Department of Hematology and Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 682-714, Republic of Korea.
Eui-Kyu
EK
Noh
Biomedical Research Center, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 682-060, Republic of Korea.
Jeong Yi
JY
Kim
Department of Hematology and Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 682-714, Republic of Korea.
Jae-Cheol
JC
Jo
Department of Hematology and Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 682-714, Republic of Korea.
Yunsuk
Y
Choi
Department of Hematology and Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 682-714, Republic of Korea.
SuJin
S
Koh
Department of Hematology and Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 682-714, Republic of Korea.
Jin Ho
JH
Baek
Department of Hematology and Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 682-714, Republic of Korea.
Young Joo
YJ
Min
Division of Hematology and Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon 405-760, Republic of Korea. Electronic address: kimhawkmd@gmail.com.
Hawk
H
Kim
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001549:Benzamides / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D005260:Female; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D011719:Pyrazines / Q000494:pharmacology* / Q000627:therapeutic use
C000606751:4-methyl-N-(3-(4-methylimidazol-1-yl)-5-trifluoromethylphenyl)-3-(4-pyrazin-2-ylpyrimidin-2-ylamino)benzamide; D001549:Benzamides; D011719:Pyrazines; D019009:Proto-Oncogene Proteins c-kit
Acute myeloid leukemia; Anti-leukemic activity; CD117; Cytotoxicity; Radotinib; Radotinib (PubChem CID: 16063245); c-KIT