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Blood, 1 August 2005, Vol. 106, No. 3, pp. 1063-1066. Prepublished online as a Blood First Edition Paper on April 19, 2005; DOI 10.1182/blood-2004-08-3225. This Article Full Text (PDF) All Versions of this Article: 2004-08-3225v1 106/3/1063    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 Sujobert, P. Articles by Bouscary, D. Search for Related Content PubMed PubMed Citation Articles by Sujobert, P. Articles by Bouscary, D. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 23, 2004 Accepted February 27, 2005 Essential role for the p110 isoform in phosphoinositide 3-kinase activation and cell proliferation in acute myeloid leukemia Pierre Sujobert, Valerie Bardet, Pascale Cornillet-Lefebvre, Joel S Hayflick, Nolwen Prie, Frederic Verdier, Bart Vanhaesebroeck, Odile Muller, Florence Pesce, Norbert Ifrah, Mathilde Hunault-Berger, Christian Berthou, Bruno Villemagne, Eric Jourdan, Bruno Audhui, Eric Solary, Brigitte Witz, Jean Luc Harousseau, Chantal Himberlin, Thierry Lamy, Bruno Lioure, Jean Yves Cahn, Francois Dreyfus, Patrick Mayeux, Catherine Lacombe, and Didier Bouscary* Departement d'Hematologie, INSERM U567, CNRS UMR 8104, Universite Paris 5, Institut Cochin, Paris, France Departement d'Hematologie, INSERM U567, CNRS UMR 8104, Universite Paris 5, Institut Cochin, Paris, France; Service d'Hematologie, Hopital Cochin, AP-HP, Paris, France Laboratoire d'Hematologie, Hopital de Reims, Reims, France ICOS Corporation, Washington, USA Ludwig Institute for Cancer Research, London, United Kingdom; Department of Biochemistry and Molecular Biology, University College London, London, United Kingdom Departement de Statistique, Hopital Cochin, Paris, France Groupe Ouest-Est des Leucemies et des Autres Maladies du Sang (GOELAMS), Reims, France * Corresponding author; email: bouscary{at}cochin.inserm.fr. The phosphoinositide 3-kinase (PI3K)/Akt signaling pathway has been shown to be frequently activated in blast cells from patients with acute myeloid leukemia (AML) and to contribute to survival and proliferation of these cells. Of the 8 distinct mammalian isoforms of PI3K, it is the class I PI3Ks (p110alpha, p110beta, p110gamma and p110delta) that are responsible for Akt activation. It is not known which PI3K isoform is critical in AML. Here we show that the p110delta isoform of PI3K is consistently expressed at high level in blast cells from AML in contrast to the other class I isoforms, the expression of which was very variable among patients. IC87114, a p110delta-selective inhibitor, suppressed both constitutive and Flt-3-stimulated Akt activation in blasts to the same extent as LY294002, an inhibitor of all PI3K isoforms. Moreover, IC87114 inhibited AML cell proliferation without affecting the proliferation of normal hematopoietic progenitor cells. 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