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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.

 Soo-Jeong Kim  ;  Ji Eun Jang  ;  June-Won Cheong  ;  Ju-In Eom  ;  Hoi-Kyung Jeung  ;  Yundeok Kim  ;  Doh Yu Hwang  ;  Yoo Hong Min 
 Korean Journal of Hematology, Vol.47(3) : 178-185, 2012 
Journal Title
 Korean Journal of Hematology 
Issue Date
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.
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실)
Yonsei Authors
김수정(Kim, Soo Jeong)
김윤덕(Kim, Yun Deok)
민유홍(Min, Yoo Hong)
엄주인(Eom, Ju In)
장지은(Jang, Ji Eun)
정준원(Cheong, June-Won)
정회경(Jeung, Hoi Kyung)
황도유(Hwang, Doh Yu)
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