Prognostic significance of constitutive phosphatidylinositol 3-kinase/Akt and mitogen- activated protein kinase phosphorylation in acute myeloid leukemia (CROSBI ID 262638)
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Prijić, Sanja ; Ugrina, Ivo ; Labar, Boris ; Nemet, Damir ; Batinić, Josip ; Zadro, Renata ; Ries, Sunčica ; Gjadrov-Kuvedžić, Koraljka ; Davidović, Sanja ; Batinić, Drago
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Prognostic significance of constitutive phosphatidylinositol 3-kinase/Akt and mitogen- activated protein kinase phosphorylation in acute myeloid leukemia
Acute myeloid leukemia (AML) is a malignant hematopoietic disease with poor clinical course and outcome. There is a constant need for new prognostic factors that could facilitate patient risk stratification. The aim of our research was to determine the phosphorylation levels of phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK) pathways in leukemic cells, their relation to P-glycoprotein (P-gp) expression/activity and their prognostic significance in adult de novo AML. A total of 118 patients with AML were enrolled in the study. In a multivariate Cox regression analysis we found that P-gp activity and Akt phosphorylation were independent poor prognostic factors of overall survival (OS). In contrast, phosphorylated extracellular signal- regulated kinase 1/2 (ERK1/2) represented a favorable prognostic factor of OS and relapse- free survival (RFS). A negative correlation between P-gp activity and p38 phosphorylation level was found, implying a possible role of this MAPK pathway in P-gp regulation. In addition, we found correlation between Akt and p38 phosphorylation levels, indicative of co- activation of two signaling cascades in AML.
Acute myeloid leukemia ; P-glycoprotein ; PI3K/Akt and MAPK signaling pathways
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