title: Prognostic significance of constitutive phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase phosphorylation in acute myeloid leukemia.
abstract: 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.
authors.affiliation: a Clinical Unit of Cellular Immunodiagnostics and In Vitro Procedures, Clinical Department of Laboratory Diagnostics , University Hospital Center Zagreb , Zagreb , Croatia.
authors.forename: Sanja
authors.initials: S
authors.lastname: Prijić
authors.affiliation: b Genos d.o.o., Zagreb , Croatia.
authors.forename: Ivo
authors.initials: I
authors.lastname: Ugrina
authors.affiliation: c Center for Expert Medicine , Zagreb , Croatia.
authors.forename: Boris
authors.initials: B
authors.lastname: Labar
authors.affiliation: d Department of Hematology , University Hospital Center Zagreb , Zagreb , Croatia.|e School of Medicine, University of Zagreb , Zagreb , Croatia.
authors.forename: Damir
authors.initials: D
authors.lastname: Nemet
authors.affiliation: d Department of Hematology , University Hospital Center Zagreb , Zagreb , Croatia.|e School of Medicine, University of Zagreb , Zagreb , Croatia.
authors.forename: Josip
authors.initials: J
authors.lastname: Batinić
authors.affiliation: f Clinical Unit of Special and Molecular Hematology, Clinical Department of Laboratory Diagnostics , University Hospital Center Zagreb , Zagreb , Croatia.
authors.forename: Renata
authors.initials: R
authors.lastname: Zadro
authors.affiliation: g Department of Pathology and Cytology , University Hospital Center Zagreb , Zagreb , Croatia.
authors.forename: Sunčica
authors.initials: S
authors.lastname: Ries
authors.affiliation: g Department of Pathology and Cytology , University Hospital Center Zagreb , Zagreb , Croatia.
authors.forename: Koraljka
authors.initials: K
authors.lastname: Gjadrov-Kuvedžić
authors.affiliation: h Clinical Unit of Cytogenetics and FISH Diagnostics of Hemato-oncological Disease, Department of Pediatrics , University Hospital Center Zagreb , Zagreb , Croatia.
authors.forename: Sanja
authors.initials: S
authors.lastname: Davidović
authors.affiliation: a Clinical Unit of Cellular Immunodiagnostics and In Vitro Procedures, Clinical Department of Laboratory Diagnostics , University Hospital Center Zagreb , Zagreb , Croatia.|e School of Medicine, University of Zagreb , Zagreb , Croatia.
authors.forename: Drago
authors.initials: D
authors.lastname: Batinić
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D015415:Biomarkers; D005260:Female; D015870:Gene Expression; D006801:Humans; D016130:Immunophenotyping; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000401:mortality*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D011379:Prognosis; D016016:Proportional Hazards Models; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D015415:Biomarkers; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases
keywords: Acute myeloid leukemia; P-glycoprotein; PI3K/Akt and MAPK signaling pathways