Analysis of Aurora B kinase in non-Hodgkin lymphoma

作者:Ikezoe Takayuki*; Takeuchi Tamotsu; Yang Jing; Adachi Yoshihiro; Nishioka Chie; Furihata Mutsuo; Koeffler H Phillip; Yokoyama Akihito
来源:Laboratory Investigation, 2009, 89(12): 1364-1373.
DOI:10.1038/labinvest.2009.106

摘要

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, 420%) expressed Aurora B in their nuclei. On the other hand, none of the low-grade B-cell lymphoma (n = 20), 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 (P < 0.01). 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. Laboratory Investigation (2009) 89, 1364-1373; doi:10.1038/labinvest.2009.106; published online 12 October 2009

  • 出版日期2009-12