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Blood, 15 September 2007, Vol. 110, No. 6, pp. 2034-2040. Prepublished online as a Blood First Edition Paper on May 10, 2007; DOI 10.1182/blood-2007-02-073700. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-02-073700v1 110/6/2034    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Yang, J. Articles by Yokoyama, A. Search for Related Content PubMed PubMed Citation Articles by Yang, J. Articles by Yokoyama, A. Related Collections Neoplasia Apoptosis Cell Cycle Cytoskeleton Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA AZD1152, a novel and selective aurora B kinase inhibitor, induces growth arrest, apoptosis, and sensitization for tubulin depolymerizing agent or topoisomerase II inhibitor in human acute leukemia cells in vitro and in vivo Jing Yang1, Takayuki Ikezoe1, Chie Nishioka1, Taizo Tasaka2, Ayuko Taniguchi1, Yoshio Kuwayama1, Naoki Komatsu1, Kentaro Bandobashi1, Kazuto Togitani1, H. Phillip Koeffler3, Hirokuni Taguchi1, and Akihito Yokoyama1 1 Department of Hematology and Respiratory Medicine, Kochi University, Nankoku, Kochi, Japan; 2 Division of Hematology, Department of Medicine, Kawasaki Medical School, Kurashiki, Okayama, Japan; 3 Department of Hematology and Oncology, Cedars-Sinai Medical Center, University of California, Los Angeles (UCLA) School of Medicine Aurora kinases play an important role in chromosome alignment, segregation, and cytokinesis during mitosis. We have recently shown that hematopoietic malignant cells including those from acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) aberrantly expressed Aurora A and B kinases, and ZM447439, a potent inhibitor of Aurora kinases, effectively induced growth arrest and apoptosis of a variety of leukemia cells. The present study explored the effect of AZD1152, a highly selective inhibitor of Aurora B kinase, on various types of human leukemia cells. AZD1152 inhibited the proliferation of AML lines (HL-60, NB4, MOLM13), ALL line (PALL-2), biphenotypic leukemia (MV4-11), acute eosinophilic leukemia (EOL-1), and the blast crisis of chronic myeloid leukemia K562 cells with an IC50 ranging from 3 nM to 40 nM, as measured by thymidine uptake on day 2 of culture. These cells had 4N/8N DNA content followed by apoptosis, as measured by cell-cycle analysis and annexin V staining, respectively. Of note, AZD1152 synergistically enhanced the antiproliferative activity of vincristine, a tubulin depolymerizing agent, and daunorubicin, a topoisomerase II inhibitor, against the MOLM13 and PALL-2 cells in vitro. Furthermore, AZD1152 potentiated the action of vincristine and daunorubicin in a MOLM13 murine xenograft model. Taken together, AZD1152 is a promising new agent for treatment of individuals with leukemia. The combined administration of AZD1152 and conventional chemotherapeutic agent to patients with leukemia warrants further investigation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. S. Boss, J. H. Beijnen, and J. H.M. Schellens Clinical Experience with Aurora Kinase Inhibitors: A Review Oncologist, August 1, 2009; 14(8): 780 - 793. [Abstract] [Full Text] [PDF] A. G. Renner, C. Dos Santos, C. Recher, C. Bailly, L. Creancier, A. Kruczynski, B. Payrastre, and S. Manenti Polo-like kinase 1 is overexpressed in acute myeloid leukemia and its inhibition preferentially targets the proliferation of leukemic cells Blood, July 16, 2009; 114(3): 659 - 662. [Abstract] [Full Text] [PDF] A. Oke, D. Pearce, R. W. Wilkinson, C. Crafter, R. Odedra, J. Cavenagh, J. Fitzgibbon, A. T. Lister, S. Joel, and D. Bonnet AZD1152 Rapidly and Negatively Affects the Growth and Survival of Human Acute Myeloid Leukemia Cells In vitro and In vivo Cancer Res., May 15, 2009; 69(10): 4150 - 4158. [Abstract] [Full Text] [PDF] E. C. VanderPorten, P. Taverna, J. N. 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Dual Degradation of Aurora A and B Kinases by the Histone Deacetylase Inhibitor LBH589 Induces G2-M Arrest and Apoptosis of Renal Cancer Cells Clin. Cancer Res., February 1, 2009; 15(3): 840 - 850. [Abstract] [Full Text] [PDF] T. Ochi, H. Fujiwara, K. Suemori, T. Azuma, Y. Yakushijin, T. Hato, K. Kuzushima, and M. Yasukawa Aurora-A kinase: a novel target of cellular immunotherapy for leukemia Blood, January 1, 2009; 113(1): 66 - 74. [Abstract] [Full Text] [PDF] X.-B. Wan, Z.-J. Long, M. Yan, J. Xu, L.-P. Xia, L. Liu, Y. Zhao, X.-F. Huang, X.-R. Wang, X.-F. Zhu, et al. Inhibition of Aurora-A suppresses epithelial-mesenchymal transition and invasion by downregulating MAPK in nasopharyngeal carcinoma cells Carcinogenesis, October 1, 2008; 29(10): 1930 - 1937. [Abstract] [Full Text] [PDF] W. Fiskus, Y. Wang, R. Joshi, R. Rao, Y. Yang, J. Chen, R. Kolhe, R. Balusu, K. Eaton, P. Lee, et al. 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