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Prepublished online as a Blood First Edition Paper on February 20, 2003; DOI 10.1182/blood-2002-08-2623. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-08-2623v1 101/11/4547    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 Byrd, J. C. Articles by Grever, M. R. Search for Related Content PubMed PubMed Citation Articles by Byrd, J. C. Articles by Grever, M. R. Related Collections Neoplasia Apoptosis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 June 2003, Vol. 101, No. 11, pp. 4547-4550 NEOPLASIA KRN5500: a novel therapeutic agent with in vitro activity against human B-cell chronic lymphocytic leukemia cells mediates cytotoxicity via the intrinsic pathway of apoptosis John C. Byrd, David M. Lucas, Andrew P. Mone, Joshua B. Kitner, Joseph J. Drabick, and Michael R. Grever From the Division of Hematology-Oncology, Department of Medicine, The Ohio State University, Columbus; and Division of Hematology-Oncology, Department of Medicine, Walter Reed Army Medical Center, Washington, DC. Therapy of B-cell chronic lymphocytic leukemia (CLL) is currently palliative, emphasizing the need for identification of new therapies for this disease. KRN5500 is a novel agent that has a unique sensitivity pattern in the National Cancer Institute cell line screening panel, suggesting a unique mechanism of action. To assess its in vitro activity in CLL, we exposed peripheral mononuclear cells from CLL patients (n = 11) to varying concentrations of this agent. Viability of the CLL cells was reduced by 50% (LC50) at 4 hours, 24 hours, and 4 days at KRN5500 concentrations of 2.50 µM, 0.276 µM, and 0.139 µM, respectively. KRN5500 induced cellular injury via caspase-dependent apoptosis involving the intrinsic mitochondrial (caspase-9) initiating caspase and caspase-3 effector caspase; however, expression of the antiapoptotic mitochondrial membrane protein Bcl-2 was unaffected. These data demonstrate KRN5500 has significant in vitro activity against human CLL cells, thus providing support for introduction of this agent into clinical trials for patients with CLL. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. E. Battle, J. Arbiser, and D. A. Frank The natural product honokiol induces caspase-dependent apoptosis in B-cell chronic lymphocytic leukemia (B-CLL) cells Blood, July 15, 2005; 106(2): 690 - 697. [Abstract] [Full Text] [PDF] D. T. Jones, E. Addison, J. M. North, M. W. Lowdell, A. V. Hoffbrand, A. B. Mehta, K. Ganeshaguru, N. I. Folarin, and R. G. Wickremasinghe Geldanamycin and herbimycin A induce apoptotic killing of B chronic lymphocytic leukemia cells and augment the cells' sensitivity to cytotoxic drugs Blood, March 1, 2004; 103(5): 1855 - 1861. [Abstract] [Full Text] [PDF]

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