Analysis of Aurora B kinase in non-Hodgkin lymphoma.
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.
Ikezoe
Takayuki
T
Department of Hematology and Respiratory Medicine, Kochi University, Japan. ikezoet@kochi-u.ac.jp
Takeuchi
Tamotsu
T
Yang
Jing
J
Adachi
Yoshihiro
Y
Nishioka
Chie
C
Furihata
Mutsuo
M
Koeffler
H Phillip
HP
Yokoyama
Akihito
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000187:drug effects; D064107:Aurora Kinase B; D064127:Aurora Kinases; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004357:Drug Synergism; D004789:Enzyme Activation; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008228:Lymphoma, Non-Hodgkin / Q000201:enzymology*; D008875:Middle Aged; D010755:Organophosphates / Q000494:pharmacology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011799:Quinazolines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D050257:Tubulin Modulators / Q000494:pharmacology; D014750:Vincristine / Q000494:pharmacology; D055815:Young Adult
C520647:2-((3-((4-((5-(2-((3-fluorophenyl)amino)-2-oxoethyl)-1H-pyrazol-3-yl)amino)quinazolin-7-yl)oxy)propyl)(ethyl)amino)ethyl dihydrogen phosphate; D010755:Organophosphates; D011799:Quinazolines; D050257:Tubulin Modulators; D014750:Vincristine; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020169:Caspases