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Blood, 1 December 2003, Vol. 102, No. 12, pp. 4179-4186. Prepublished online as a Blood First Edition Paper on August 14, 2003; DOI 10.1182/blood-2003-03-0960. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-03-0960v1 102/12/4179    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 Carter, B. Z. Articles by Andreeff, M. Search for Related Content PubMed PubMed Citation Articles by Carter, B. Z. Articles by Andreeff, M. Related Collections Neoplasia Apoptosis Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Caspase-independent cell death in AML: caspase inhibition in vitro with pan-caspase inhibitors or in vivo by XIAP or Survivin does not affect cell survival or prognosis Bing Z. Carter, Steven M. Kornblau, Twee Tsao, Rui-Yu Wang, Wendy D. Schober, Michele Milella, Hsi-Guang Sung, John C. Reed, and Michael Andreeff From the Department of Blood and Marrow Transplantation, Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX; and The Burnham Institute, La Jolla, CA. Survivin and XIAP, members of the protein family known as the inhibitors of apoptosis, interfere with the activation of caspases, called the "cell death executioners." We examined Survivin (n = 116) and XIAP (n = 172) expression in primary acute myeloid leukemia (AML) blasts and assessed the impact of their expression on prognosis. They were detected in all samples analyzed. However, no correlation was observed with cytogenetics, remission attainment, or overall survival of patients with AML. To investigate the importance of caspases in chemotherapy-induced apoptosis in AML, we treated OCI-AML3 cells with Ara-C, doxorubicin, vincristine, and paclitaxel, which induced caspase cleavage and apoptosis. Blocking of caspase activation by pan-caspase inhibitor abolished poly(adenosine diphosphate [ADP]-ribose) polymerase cleavage and DNA fragmentation but did not prevent chemotherapy-induced cell death and did not inhibit, or only partially inhibited, mitochondrial release of cytochrome c, Smac, apoptosis-inducing factor (AIF), or loss of mitochondrial membrane potential. Caspase inhibition also did not protect AML blasts from chemotherapy-induced cell death in vitro. These results suggest that expression levels of Survivin or XIAP have no prognostic impact in AML patients. Although anticancer drugs induced caspase cleavage and apoptosis, cell killing was caspase independent. This may partially explain the lack of prognostic impact of XIAP and Survivin and may suggest caspase-independent mechanisms of cell death in AML. (Blood. 2003;102:4179-4186) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. Z. Carter, D. H. Mak, W. D. Schober, M. F. Dietrich, C. Pinilla, L. T. Vassilev, J. C. Reed, and M. Andreeff Triptolide sensitizes AML cells to TRAIL-induced apoptosis via decrease of XIAP and p53-mediated increase of DR5 Blood, April 1, 2008; 111(7): 3742 - 3750. [Abstract] [Full Text] [PDF] D. Vucic and W. J. 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