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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
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 inhibit...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Korean Society of Hematology; Korean Society of Blood and Marrow Transplantation; Korean Society of Pediatric Hematology-Oncology; Korean Society on Thrombosis and Hemostasis
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3464334/ https://www.ncbi.nlm.nih.gov/pubmed/23071472 http://dx.doi.org/10.5045/kjh.2012.47.3.178 |
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author | Kim, Soo-Jeong Jang, Ji Eun Cheong, June-Won Eom, Ju-In Jeung, Hoi-Kyung Kim, Yundeok Hwang, Doh Yu Min, Yoo Hong |
author_facet | Kim, Soo-Jeong Jang, Ji Eun Cheong, June-Won Eom, Ju-In Jeung, Hoi-Kyung Kim, Yundeok Hwang, Doh Yu Min, Yoo Hong |
author_sort | Kim, Soo-Jeong |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3464334 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Korean Society of Hematology; Korean Society of Blood and Marrow Transplantation; Korean Society of Pediatric Hematology-Oncology; Korean Society on Thrombosis and Hemostasis |
record_format | MEDLINE/PubMed |
spelling | pubmed-34643342012-10-15 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 Kim, Soo-Jeong Jang, Ji Eun Cheong, June-Won Eom, Ju-In Jeung, Hoi-Kyung Kim, Yundeok Hwang, Doh Yu Min, Yoo Hong Korean J Hematol Original Article 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. Korean Society of Hematology; Korean Society of Blood and Marrow Transplantation; Korean Society of Pediatric Hematology-Oncology; Korean Society on Thrombosis and Hemostasis 2012-09 2012-09-25 /pmc/articles/PMC3464334/ /pubmed/23071472 http://dx.doi.org/10.5045/kjh.2012.47.3.178 Text en © 2012 Korean Society of Hematology http://creativecommons.org/licenses/by-nc/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Kim, Soo-Jeong Jang, Ji Eun Cheong, June-Won Eom, Ju-In Jeung, Hoi-Kyung Kim, Yundeok Hwang, Doh Yu Min, Yoo Hong 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 |
title | 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 |
title_full | 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 |
title_fullStr | 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 |
title_full_unstemmed | 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 |
title_short | 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 |
title_sort | 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 |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3464334/ https://www.ncbi.nlm.nih.gov/pubmed/23071472 http://dx.doi.org/10.5045/kjh.2012.47.3.178 |
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