Aurora A kinase expression is increased in leukemia stem cells, and a selective Aurora A kinase inhibitor enhances Ara-C-induced apoptosis in acute myeloid leukemia stem cells.
10.5045/kjh.2012.47.3.178
- Author:
Soo Jeong KIM
1
;
Ji Eun JANG
;
June Won CHEONG
;
Ju In EOM
;
Hoi Kyung JEUNG
;
Yundeok KIM
;
Doh Yu HWANG
;
Yoo Hong MIN
Author Information
1. Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea. minbrmmnd@yuhs.ac
- Publication Type:Original Article
- Keywords:
Acute myeloid leukemia;
Leukemia stem cell;
Aurora kinase
- MeSH:
Apoptosis;
Cell Death;
Cell Line;
Cytarabine;
Epilepsy;
Granulocyte Colony-Stimulating Factor;
Hematopoietic Stem Cells;
Humans;
Leukemia;
Leukemia, Myeloid, Acute;
Neoplastic Stem Cells;
Phosphotransferases;
Protein-Serine-Threonine Kinases;
Stem Cells
- From:Korean Journal of Hematology
2012;47(3):178-185
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND: The overexpression of Aurora A kinase (AurA) has been reported in various malignancies, including acute myeloid leukemia (AML). However, the expression of AurA and the effects of AurA inhibition in cancer stem cells are not yet fully understood. We investigated the expression and inhibition of AurA in AML stem cells (CD34+/CD38-). METHODS: Expression of AurA was investigated in cell lines (NB4 and KG1) that express high levels of CD34 and low levels of CD38. Primary AML cells were harvested from 8 patients. The expression of AurA and cell death induced by inhibition of AurA were analyzed in CD34+/CD38- cells. RESULTS: AurA was shown to be overexpressed in both primary AML cells and leukemia stem cells (LSCs) compared to normal hematopoietic stem cells. Inhibition of AurA plus cytarabine treatment in LSCs resulted in increased cytotoxicity compared to cytarabine treatment alone. Additional stimulation with granulocyte-colony stimulating factor (G-CSF) increased the cell death caused by AurA inhibition plus cytarabine treatment. CONCLUSION: To our knowledge, this is the first report describing increased expression of AurA in LSCs. Our results suggest that selective AurA inhibition may be used to reduce LSCs, and this reduction may be enhanced by stimulation with G-CSF. Further exploration of relationship between nuclear factor kappa-B and AurA inhibition and the potential of AurA inhibition for use in leukemia treatment is needed.
