Analysis of Aurora B kinase in non-Hodgkin lymphoma
Analysis of Aurora B kinase in non-Hodgkin lymphoma
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DOI：
10.1038/labinvest.2009.106
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发表时间：
2009-12-01
影响因子：
5
通讯作者：
Yokoyama, Akihito
中科院分区：
文献类型：
--
作者：
Ikezoe, Takayuki;Takeuchi, Tamotsu;Yokoyama, Akihito
本研究探讨了极光B，有丝分裂的关键调节，在71个淋巴结和肿瘤标本手术切除的个人与各种类型的非霍奇金淋巴瘤（NHL）的水平。免疫组化结果显示，弥漫性大B细胞淋巴瘤（10/21，48%）和伯基特淋巴瘤（6/7，86%）细胞核内均高度表达Aurora B（阳性细胞百分率420%）。另一方面，除1例滤泡性淋巴瘤外，低级别B细胞淋巴瘤（n = 20）均未高表达该蛋白激酶，提示Aurora B水平与B细胞NHL的组织学分级相关（P < 0.01）。AZD 1152-HQPA是Aurora B激酶的一种选择性抑制剂，体外暴露于BL/白血病细胞可有效诱导细胞生长停滞和凋亡，其作用方式既依赖于半胱天冬酶，也不依赖于半胱天冬酶。此外，AZD 1152协同增强长春新碱（VCR）诱导这些细胞生长停滞的作用。进一步的实验发现，VCR通过激活c-Jun N-末端激酶增加p-Aurora B的水平，在存在AZD 1152-HQPA的情况下，c-Jun N-末端激酶被阻断。实验室调查（2009）89，1364-1373; doi：10.1038/labinvest.2009.106;在线发表2009年10月12日
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