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Constitutive phosphoinositide 3-kinase activation in acute myeloid leukemia is not due to p110δ mutations

Leukemia volume 20, pages 374–376 (2006)Cite this article

The phosphoinositide 3-kinase (PI3K)/AKT signaling pathway is activated in acute myeloid leukemia (AML) and may control both proliferation and apoptosis of leukemic progenitor cells.1 The mechanisms leading to PI3K activation are unknown. Class IA PI3K are heterodimeric enzymes composed of a p110 catalytic subunit associated to a regulatory p85 subunit, and signal downstream of tyrosine kinases (TK) and Ras. Three p110 isoforms (α,β,δ) have been cloned that display many common structural and functional properties.2, 3 We recently reported that the p110δ isoform is expressed at high level in AML blast cells, whereas expression of α and β isoforms is variable between patients.4 Moreover, the p110δ isoform is the main contributor of PI3K activity in AML blasts, as demonstrated by the complete inhibition of AKT phosphorylation induced by IC87114, a selective p110δ inhibitor.4

Activating mutations in the PI3KCA gene of class IA PI3Ks have been described in solid tumors.5 These mutations are clustered in exons 9 and 20, coding for the helical and the kinase domains of the p110α protein, with rare mutations in the p85 binding domain and in the C2 domain.5 These mutants are oncogenic and can promote growth and invasion of human cancer cells, by activating the AKT pathway and the target of rapamycin (TOR) kinase.6, 7

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Authors and Affiliations

  1. Laboratoire d'Hématologie. CHU, Reims, France

    P Cornillet-Lefebvre, W Cuccuini, L Gillot & P Nguyen

  2. UPRES EA 3796, IFR 53, Faculté de Médecine, Reims, France

    P Cornillet-Lefebvre, W Cuccuini, L Gillot & P Nguyen

  3. Université Paris-Descartes. Faculté de Médecine, Institut Cochin (INSERM U567, CNRS-UMR 8104), Hôpital Cochin, Paris, France

    V Bardet, J Tamburini, F Dreyfus, P Mayeux, C Lacombe & D Bouscary

  4. AP-HP, Service d'Hématologie, Hôpital Cochin, Paris, France

    V Bardet, J Tamburini, F Dreyfus, P Mayeux, C Lacombe & D Bouscary

  5. Service des Maladies du Sang. CHU Angers, Angers, France

    N Ifrah

  6. UPRES EA 3863 UFR Médecine Angers, Angers, France

    N Ifrah

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  1. P Cornillet-Lefebvre
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  2. W Cuccuini
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Correspondence to D Bouscary.

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Cornillet-Lefebvre, P., Cuccuini, W., Bardet, V. et al. Constitutive phosphoinositide 3-kinase activation in acute myeloid leukemia is not due to p110δ mutations. Leukemia 20, 374–376 (2006). https://doi.org/10.1038/sj.leu.2404054

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