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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 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 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 Frelin, C. Articles by Peyron, J.-F. Search for Related Content PubMed PubMed Citation Articles by Frelin, C. Articles by Peyron, J.-F. Related Collections Neoplasia Apoptosis Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Targeting NF-B activation via pharmacologic inhibition of IKK2-induced apoptosis of human acute myeloid leukemia cells Catherine Frelin, Véronique Imbert, Emmanuel Griessinger, Annie-Claude Peyron, Nathalie Rochet, Patrick Philip, Christian Dageville, Anne Sirvent, Michaël Hummelsberger, Etienne Bérard, Michel Dreano, Nicolas Sirvent, and Jean-François Peyron From the Institut National de la Santé et de la Recherche Médicale (INSERM) U526, Physiopathologie de la Survie et de la Mort Cellulaires et Infections Virales, France; Centre National de la Recherche Scientifique (CNRS) Unité Mixté de Recherche (UMR) 6549, Instabilité et Altération des Génomes, France; Service de Pédiatrie and Service d'Hématologie, Hôpital de l'Archet II, Nice, France; Serono International, Geneva, Switzerland; Unité d'exploration fonctionnelle cellulaire et tissulaire (UEFCT), Hôpital Pasteur, Nice, France; and Institut Fédératif de Recherche (IFR) 50, Génétique et Signalisation Moléculaires, Faculté de Médecine Pasteur, Nice, France. Acute myeloid leukemia (AML) cells are characterized by a constitutive and abnormal activation of the nuclear factor-B (NF-B) transcription factor. This study, conducted in vitro on 18 patients, shows that targeting the IKB kinase 2 (IKK2) kinase with the specific pharmacologic 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 etoposide (VP16). 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: D. Briot, G. Mace-Aime, F. Subra, and F. 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