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Prepublished online as a Blood First Edition Paper on August 14, 2003; DOI 10.1182/blood-2003-03-0960. This Article 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 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. Social Bookmarking                   What's this? Submitted March 28, 2003 Accepted August 4, 2003 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* Department of Blood and Marrow Transplantation, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA Department of Biostatistics, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA The Burnham Institute, La Jolla, CA, USA * Corresponding author; email: mandreef{at}mdanderson.org. Survivin and XIAP, members of the "Inhibitors of Apoptosis" proteins family, interfere with activation of caspases, 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 AML patients. To investigate the importance of caspases in chemotherapy-induced apoptosis in AML, we treated OCI-AML3 cells with Ara-C, doxorubicin, vincristine, and Taxol which induced caspase cleavage and apoptosis. Blocking of caspase activation by pan-caspase inhibitor abolished poly (ADP-ribose) polymerase cleavage and DNA fragmentation, but did not prevent chemotherapy-induced cell death and did not or only partially inhibited mitochondrial release of cytochrome C, Smac, 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. 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