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Blood, 1 November 2004, Vol. 104, No. 9, pp. 2873-2878. Prepublished online as a Blood First Edition Paper on July 8, 2004; DOI 10.1182/blood-2003-10-3720. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-10-3720v1 104/9/2873    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 Shah, N. Articles by LeBien, T. W. Search for Related Content PubMed PubMed Citation Articles by Shah, N. Articles by LeBien, T. W. Related Collections Immunobiology Neoplasia Apoptosis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Enhancement of stress-induced apoptosis in B-lineage cells by caspase-9 inhibitor Nisha Shah, Rebecca J. Asch, Alana S. Lysholm, and Tucker W. LeBien From the Cancer Center and Department of Laboratory Medicine/Pathology, University of Minnesota, Minneapolis, MN. We have established human B-lineage (BLIN) acute lymphoblastic leukemia cell lines that retain a dependency on fibroblast monolayers for survival and proliferation. Eight hours following removal from adherent cell contact BLIN cells undergo a decrease in mitochondrial transmembrane potential and an increase in annexin V binding. Unexpectedly, the caspase-9 inhibitor (C9i) benzyloxycarbonyl-Leu-Glu-His-Asp-fluoromethylketone enhanced the appearance of apoptotic cells within 8 hours following removal of BLIN cells from fibroblast monolayers. C9i enhancement of apoptosis was dose dependent and did not occur with irreversible inhibitors of caspases-2, -3, -6, and -8. C9i also enhanced apoptosis in cord blood-derived CD19+ B-lineage cells (but not myeloid cells) removed from murine stromal cells. Longer exposure (> 18 hours) to C9i culminated in apoptosis in a panel of B-lineage acute lymphoblastic leukemia (ALL) cell lines in the presence or absence of fibroblast monolayers, as well as in 2 proliferating leukemic cell lines (RAMOS and CEM). BLIN-4L cells made deficient in caspase-9 by RNA interference exhibited no resistance to apoptotic signals and actually showed increased apoptotic sensitivity to staurosporine. These collective results suggest that a 4-amino acid caspase inhibitor of caspase-9 can promote apoptosis and that at least some types of apoptotic pathways in B-lineage ALL do not require caspase-9. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. Hermanson, S. N. Addo, A. A. Bajer, J. S. Marchant, S. G. K. Das, B. Srinivasan, F. Al-Mousa, F. Michelangeli, D. D. Thomas, T. W. LeBien, et al. Dual Mechanisms of sHA 14-1 in Inducing Cell Death through Endoplasmic Reticulum and Mitochondria Mol. Pharmacol., September 1, 2009; 76(3): 667 - 678. [Abstract] [Full Text] [PDF] M. E. Lasbury, P. J. Durant, C. A. Ray, D. Tschang, R. Schwendener, and C.-H. Lee Suppression of Alveolar Macrophage Apoptosis Prolongs Survival of Rats and Mice with Pneumocystis Pneumonia. J. Immunol., June 1, 2006; 176(11): 6443 - 6453. [Abstract] [Full Text] [PDF]

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