Resistance to Imatinib Mesylate-induced apoptosis in acute lymphoblastic leukemia is associated with PTEN down-regulation due to promoter hypermethylation
Keywords: 
PTEN
Ph+ ALL
Imatinib
PI3K AKT
Materias Investigacion::Ciencias de la Salud::Oncología
Issue Date: 
2008
Publisher: 
Elsevier
ISSN: 
0145-2126
Citation: 
Montiel-Duarte, C., Cordeu, L., Agirre, X., Roman-Gomez, J. et al. Resistance to Imatinib Mesylate-induced apoptosis in acute lymphoblastic leukemia is associated with PTEN down-regulation due to promoter hypermethylation. Leukemia Research 2008; 32 (5): 709–716
Abstract
The aim of our study was to determine the potential mechanism(s) implicated in Imatinib resistance in patients with Ph+ ALL. Resistance of Ph+ ALL cells to Imatinib-induced apoptosis was associated with lack of inhibition of Akt phosphorylation. Addition of the PI3K inhibitor LY294002 to Imatinib significantly increased apoptosis of Ph+ ALL cells. Interestingly, expression of PTEN was reduced in Ph+ ALL cells whichwas due to PTEN promoter hypermethylation. Treatment of Ph+ ALLcells with 5-Aza-2 -deoxycytidinewas associated with an increased expression of PTEN and an increase in cell apoptosis. These results suggest that Imatinib resistance in patients with ALL may be dependent at least in part to PTEN down-regulation due to the abnormal promoter hypermethylation and support the potential role of de-methylating agents for the treatment of patients with Ph+ ALL.

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