SEARCH:   Advanced

Prepublished online as a Blood First Edition Paper on February 20, 2003; DOI 10.1182/blood-2002-08-2623. This Article 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 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 Social Bookmarking                   What's this? Submitted September 4, 2002 Accepted January 15, 2003 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 Mone, Joshua B Kitner, Joseph J Drabick, and Michael R Grever Department of Medicine, The Ohio State University, Columbus, OH Department of Medicine, Walter Reed Army Medical Center, Washington, DC * Corresponding author; email: byrd-3{at}medctr.osu.edu. 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 percent (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 anti-apoptotic 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]

	Copyright © 2003 by American Society of Hematology         Online ISSN: 1528-0020