TY - JOUR
T1 - Analysis of Aurora B kinase in non-Hodgkin lymphoma
AU - Ikezoe, Takayuki
AU - Takeuchi, Tamotsu
AU - Yang, Jing
AU - Adachi, Yoshihiro
AU - Nishioka, Chie
AU - Furihata, Mutsuo
AU - Koeffler, H. Phillip
AU - Yokoyama, Akihito
N1 - Funding Information:
We thank Dr Kirsten Mundt (AstraZeneca Pharmaceuticals, UK) for providing AZD1152-HQPA. This work was supported in part by grant-in-aid from the Ministry of Education, Culture Sports, Science and Technology of Japan (to T.I), the Kochi University President’s Discretionary grant (to TI), Takeda Science Foundation (to TI), Sagawa Foundation for Promotion of Cancer Research (to TI) and Sheryl Weissberg Lymphoma Research Foundation (to HPK). TI contributed to the concept and design, performed the experiments, interpreted and analyzed the data, and wrote the article. TT, YA and MT performed the histological examination. CN and JY performed the experiments. HPH provided critical revision and intellectual content. AY provided important intellectual content and gave final approval.
PY - 2009/12
Y1 - 2009/12
N2 - This study explored the levels of Aurora B, a key regulator of mitosis, in 71 lymph nodes and tumor specimens excised operatively from individuals with various types of non-Hodgkin lymphoma (NHLs). Immunohistochemical examination found that diffuse large B-cell lymphoma (10/21, 48%) and Burkitt lymphoma (BL) (6/7, 86%) cells highly (percentage of positive cells, 20%) expressed Aurora B in their nuclei. On the other hand, none of the low-grade B-cell lymphoma (n20), except for one case of follicular lymphoma, highly expressed this protein kinase, suggesting that levels of Aurora B correlated with histological grade in B-cell NHLs (P0.01). Exposure of BL/leukemia cells to AZD1152-HQPA in vitro, a selective inhibitor of Aurora B kinase, potently induced growth arrest and apoptosis in a caspase-dependent, as well as-independent manner. Moreover, AZD1152 synergistically enhanced the effects of vincristine (VCR) to induce growth arrest of these cells. Further experiments found that VCR increased levels of the p-Aurora B through the activation of c-Jun N-terminal kinase, which was blocked in the presence of AZD1152-HQPA.
AB - This study explored the levels of Aurora B, a key regulator of mitosis, in 71 lymph nodes and tumor specimens excised operatively from individuals with various types of non-Hodgkin lymphoma (NHLs). Immunohistochemical examination found that diffuse large B-cell lymphoma (10/21, 48%) and Burkitt lymphoma (BL) (6/7, 86%) cells highly (percentage of positive cells, 20%) expressed Aurora B in their nuclei. On the other hand, none of the low-grade B-cell lymphoma (n20), except for one case of follicular lymphoma, highly expressed this protein kinase, suggesting that levels of Aurora B correlated with histological grade in B-cell NHLs (P0.01). Exposure of BL/leukemia cells to AZD1152-HQPA in vitro, a selective inhibitor of Aurora B kinase, potently induced growth arrest and apoptosis in a caspase-dependent, as well as-independent manner. Moreover, AZD1152 synergistically enhanced the effects of vincristine (VCR) to induce growth arrest of these cells. Further experiments found that VCR increased levels of the p-Aurora B through the activation of c-Jun N-terminal kinase, which was blocked in the presence of AZD1152-HQPA.
KW - AZD1152
KW - Apoptosis
KW - Aurora B
KW - Burkitt lymphoma
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U2 - 10.1038/labinvest.2009.106
DO - 10.1038/labinvest.2009.106
M3 - Article
C2 - 19823168
AN - SCOPUS:70549111347
SN - 0023-6837
VL - 89
SP - 1364
EP - 1373
JO - Laboratory Investigation
JF - Laboratory Investigation
IS - 12
ER -