Analysis of Aurora B kinase in non-Hodgkin lymphoma

Lab Invest. 2009 Dec;89(12):1364-73. doi: 10.1038/labinvest.2009.106. Epub 2009 Oct 12.

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 (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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis / drug effects
  • Aurora Kinase B
  • Aurora Kinases
  • Caspases / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Synergism
  • Enzyme Activation
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Lymphoma, Non-Hodgkin / enzymology*
  • Middle Aged
  • Organophosphates / pharmacology
  • Phosphorylation
  • Protein Serine-Threonine Kinases / antagonists & inhibitors
  • Protein Serine-Threonine Kinases / metabolism*
  • Quinazolines / pharmacology
  • Signal Transduction / drug effects
  • Tubulin Modulators / pharmacology
  • Vincristine / pharmacology
  • Young Adult

Substances

  • 2-((3-((4-((5-(2-((3-fluorophenyl)amino)-2-oxoethyl)-1H-pyrazol-3-yl)amino)quinazolin-7-yl)oxy)propyl)(ethyl)amino)ethyl dihydrogen phosphate
  • Organophosphates
  • Quinazolines
  • Tubulin Modulators
  • Vincristine
  • AURKB protein, human
  • Aurora Kinase B
  • Aurora Kinases
  • Protein Serine-Threonine Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Caspases