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Blood, 1 August 2007, Vol. 110, No. 3, pp. 1025-1028.
Prepublished online as a Blood First Edition Paper on April 10, 2007; DOI 10.1182/blood-2006-12-061283.


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NEOPLASIA

Brief Report

Constitutive phosphoinositide 3-kinase/Akt activation represents a favorable prognostic factor in de novo acute myelogenous leukemia patients

Jerome Tamburini1,4,6, Caroline Elie4,7, Valérie Bardet1,5, Nicolas Chapuis1,4, Sophie Park1,4,6, Philippe Broët8, Pascale Cornillet-Lefebvre9, Bruno Lioure10, Valérie Ugo11, Odile Blanchet12, Norbert Ifrah13, Francis Witz14, François Dreyfus1,4,6, Patrick Mayeux1,4, Catherine Lacombe1,5, and Didier Bouscary1,4,6

1 Institut Cochin, Département d'Hématologie, Paris; 2 Institut National de la Santé et de la Recherche Médicale (INSERM), U567, Paris; 3 Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche (UMR) 8104, Paris; 4 Université Paris Descartes, Faculté de Médecine René Descartes, Unité Mixte de Recherche (UMR)-S 8104, Paris; 5 Laboratoire d'Hématologie, Assistance Publique–Hôpitaux de Paris, Hôpital Cochin, Paris; 6 Service de Médecine Interne–Hématologie, Assistance Publique–Hôpitaux de Paris, Hôpital Cochin, Paris; 7 Département de Biostatistique, Hôpital Cochin, Paris; 8 JE 2492, Faculté de Médecine Paris Sud; 9 Laboratoire d'Hématologie, Centre Hospitalo–Universitaire (CHU) Reims; 10 Département d'Hématologie et d'Oncologie, Hôpitaux Universitaires, Strasbourg; 11 Laboratoire d'Hématologie, CHU Brest; 12 Laboratoire d'Hématologie, CHU Angers; 13 Service des Maladies du Sang, CHU Angers; 14 Service d'Hématologie, Hôpital Brabois, Nancy, France

The phosphoinositide 3-kinase (PI3K/Akt) pathway is activated in acute myelogenous leukemia (AML) and is promising for targeted inhibition. Ninety-two patients with primary AML were analyzed for PI3K/Akt constitutive activation. Fifty percent of the patients presented with constitutive PI3K activation (PI3K +). No difference was observed between PI3K + and PI3K groups concerning age, sex, white blood cell count, lactate dehydrogenase (LDH) level, bone marrow blast cells, French-American-British (FAB) classification, cytogenetics, RAS or nucleophosmin (NPM) mutations. Slightly more FLT3-ITD was detected in the PI3K group (P = .048). The complete remission rate was similar between the 2 groups. With a median follow-up of 26 months, we observed for PI3K + and PI3K patients, respectively, 56% and 33% overall survival (P = .001) and 72% and 41% relapse-free survival (P = .001). Constitutive PI3K/Akt activity is a favorable prognosis factor in AML, even after adjustment for FLT3-ITD, and may confer a particular sensitivity to chemotherapy. A better understanding of the downstream effectors of the PI3K/Akt pathway is needed before targeting in AML.


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