title: Constitutive phosphoinositide 3-kinase/Akt activation represents a favorable prognostic factor in de novo acute myelogenous leukemia patients.
abstract: 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.
authors.affiliation: Department d'Hematologie, Institut Cochin, 27 rue Faubourg Saint-Jacques, F-75014 Paris, France.
authors.forename: Jerome
authors.initials: J
authors.lastname: Tamburini
authors.forename: Caroline
authors.initials: C
authors.lastname: Elie
authors.forename: Valérie
authors.initials: V
authors.lastname: Bardet
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chapuis
authors.forename: Sophie
authors.initials: S
authors.lastname: Park
authors.forename: Philippe
authors.initials: P
authors.lastname: Broët
authors.forename: Pascale
authors.initials: P
authors.lastname: Cornillet-Lefebvre
authors.forename: Bruno
authors.initials: B
authors.lastname: Lioure
authors.forename: Valérie
authors.initials: V
authors.lastname: Ugo
authors.forename: Odile
authors.initials: O
authors.lastname: Blanchet
authors.forename: Norbert
authors.initials: N
authors.lastname: Ifrah
authors.forename: Francis
authors.initials: F
authors.lastname: Witz
authors.forename: François
authors.initials: F
authors.lastname: Dreyfus
authors.forename: Patrick
authors.initials: P
authors.lastname: Mayeux
authors.forename: Catherine
authors.initials: C
authors.lastname: Lacombe
authors.forename: Didier
authors.initials: D
authors.lastname: Bouscary
mesh_terms: D001752:Blast Crisis / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000401:mortality; D001853:Bone Marrow / Q000201:enzymology / Q000473:pathology; D018572:Disease-Free Survival; D004789:Enzyme Activation / Q000235:genetics; D005260:Female; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000401:mortality; D007958:Leukocyte Count; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D000090243:Nucleophosmin; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D015996:Survival Rate; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D007770:L-Lactate Dehydrogenase; D009687:Nuclear Proteins; D000090243:Nucleophosmin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051941:fms-Like Tyrosine Kinase 3; D018631:ras Proteins; C000716967:NPM1 protein, human; C497970:FLT3 protein, human