Analysis of Aurora B kinase in non-Hodgkin lymphoma

Takayuki Ikezoe, Tamotsu Takeuchi, Jing Yang, Yoshihiro Adachi, Chie Nishioka, Mutsuo Furihata, H. Phillip Koeffler, Akihito Yokoyama

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1364-1373
Number of pages10
JournalLaboratory Investigation
Volume89
Issue number12
DOIs
StatePublished - Dec 2009
Externally publishedYes

Keywords

  • AZD1152
  • Apoptosis
  • Aurora B
  • Burkitt lymphoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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