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Blood, 15 January 2005, Vol. 105, No. 2, pp. 804-811. Prepublished online as a Blood First Edition Paper on September 28, 2004; DOI 10.1182/blood-2004-04-1463. This Article Full Text (PDF) All Versions of this Article: 2004-04-1463v1 105/2/804    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 Frelin, C. Articles by Peyron, J.-F. Search for Related Content PubMed PubMed Citation Articles by Frelin, C. Articles by Peyron, J.-F. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 19, 2004 Accepted August 31, 2004 Targeting NF-B activation via pharmacological inhibition of IKK2 induced apoptosis of human acute myeloid leukemia cells Catherine Frelin, Veronique Imbert, Emmanuel Griessinger, Annie-Claude Peyron, Nathalie Rochet, Patrick Philip, Christian Dageville, Anne Sirvent, Michael Hummelsberger, Etienne Berard, Michel Dreano, Nicolas Sirvent, and Jean-Francois Peyron* Faculte de Medecine Pasteur, INSERM U526 "Physiopathologie de la Survie et de la Mort Cellulaires et Infections Virales", Nice, France; "Genetique et Signalisation Moleculaires", IFR50, Faculte de Medecine Pasteur, Nice, France UEFCT, Hopital Pasteur, Nice, France "Instabilite et Alteration des Genomes", Faculte de Medecine Pasteur, CNRS, UMR6549, Nice, France; "Genetique et Signalisation Moleculaires", IFR50, Faculte de Medecine Pasteur, Nice, France Service de Pediatrie, Hopital de l'Archet II, CHU, Nice, France Service de Hematologie, Hopital de l'Archet II, CHU, Nice, France Serono International SA, Geneva, Switzerland * Corresponding author; email: peyron{at}unice.fr. Acute Myeloid Leukemia (AML) cells are characterized by a constitutive and abnormal activation of the NF-B transcription factor. This study conducted in vitro on 18 patients, shows that targeting the IKK2 kinase with the specific pharmacological inhibitor AS602868 to block NF-B activation, led to apoptosis of human primary AML cells. Moreover, AS602868 potentiated the apoptotic response induced by the current chemotherapeutic drugs doxorubicin, cytarabine or VP-16. AS602868-induced cell death was associated with rupture of the mitochondrial transmembrane potential and activation of cellular caspases. NF-B inhibition did not affect normal CD34+ hematopoietic precursors, suggesting that it could represent a new adjuvant strategy for AML treatment. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. K. Kiessling, C. D. Klemke, M. M. Kaminski, I. E. Galani, P. H. Krammer, and K. 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