Essential role for the p110delta isoform in phosphoinositide 3-kinase activation and cell proliferation in acute myeloid leukemia - PubMed (original) (raw)

. 2005 Aug 1;106(3):1063-6.

doi: 10.1182/blood-2004-08-3225. Epub 2005 Apr 19.

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 Audhuy, Eric Solary, Brigitte Witz, Jean Luc Harousseau, Chantal Himberlin, Thierry Lamy, Bruno Lioure, Jean Yves Cahn, Francois Dreyfus, Patrick Mayeux, Catherine Lacombe, Didier Bouscary

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• PMID: 15840695
• DOI: 10.1182/blood-2004-08-3225

Free article

Essential role for the p110delta isoform in phosphoinositide 3-kinase activation and cell proliferation in acute myeloid leukemia

Pierre Sujobert et al. Blood. 2005.

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Abstract

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 a 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. These observations identify p110delta as a potential therapeutic target in AML.

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