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This Article Full Text Full Text (PDF) 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 Milella, M. Articles by Andreeff, M. Search for Related Content PubMed PubMed Citation Articles by Milella, M. Articles by Andreeff, M. Related Collections Neoplasia Apoptosis Signal Transduction Brief Reports Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 May 2002, Vol. 99, No. 9, pp. 3461-3464 BRIEF REPORT Synergistic induction of apoptosis by simultaneous disruption of the Bcl-2 and MEK/MAPK pathways in acute myelogenous leukemia Michele Milella, Zeev Estrov, Steven M. Kornblau, Bing Z. Carter, Marina Konopleva, Ana Tari, Wendy D. Schober, David Harris, Clinton E. Leysath, Gabriel Lopez-Berestein, Ziwei Huang, and Michael Andreeff From the Department of Blood and Marrow Transplantation, Section of Molecular Hematology and Therapy, and Department of Bioimmunotherapy, The University of Texas M. D. Anderson Cancer Center, Houston, TX; and Department of Biochemistry, University of Illinois at Urbana-Champaign, Champaign, IL. Recent studies suggest that the Bcl-2 and mitogen-activated protein kinase (MAPK) pathways together confer an aggressive, apoptosis-resistant phenotype on acute myelogenous leukemia (AML) cells. In this study, we analyzed the effects of simultaneous inhibition of these 2 pathways. In AML cell lines with constitutively activated MAPK, MAPK kinase (MEK) blockade by PD184352 strikingly potentiated the apoptosis induced by the small-molecule Bcl-2 inhibitor HA14-1 or by Bcl-2 antisense oligonucleotides. Isobologram analysis confirmed the synergistic nature of this interaction. Moreover, MEK blockade overcame Bcl-2 overexpression-mediated resistance to the proapoptotic effects of HA14-1. Most importantly, simultaneous exposure to PD184352 significantly (P = .01) potentiated HA14-1-mediated inhibition of clonogenic growth in all primary AML samples tested. These findings show that the Bcl-2 and MAPK pathways are relevant molecular targets in AML and that their concurrent inhibition could be developed into a new therapeutic strategy for this disease. © 2002 by The American Society of Hematology.   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. 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