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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
Korean Journal of Hematology ; : 178-185, 2012.
Artículo en Inglés | WPRIM | ID: wpr-720172
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.
Asunto(s)

Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Fosfotransferasas / Células Madre / Células Madre Neoplásicas / Células Madre Hematopoyéticas / Leucemia Mieloide Aguda / Leucemia / Línea Celular / Factor Estimulante de Colonias de Granulocitos / Muerte Celular / Proteínas Serina-Treonina Quinasas Límite: Humanos Idioma: Inglés Revista: Korean Journal of Hematology Año: 2012 Tipo del documento: Artículo

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Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Fosfotransferasas / Células Madre / Células Madre Neoplásicas / Células Madre Hematopoyéticas / Leucemia Mieloide Aguda / Leucemia / Línea Celular / Factor Estimulante de Colonias de Granulocitos / Muerte Celular / Proteínas Serina-Treonina Quinasas Límite: Humanos Idioma: Inglés Revista: Korean Journal of Hematology Año: 2012 Tipo del documento: Artículo