Biomedical papers, 2016 (vol. 160), issue 1

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2016, 160(1):94-99 | 10.5507/bp.2015.036

Evaluation of cytokines and soluble adhesion molecules in patients with newly diagnosed acute myeloid leukemia: the role of TNF-alpha and FLT3-ITD

Tomas Kupsaa,b, Jan Vanekc, Martina Vasatovad, Iva Karesovad, Pavel Zakb, Ladislav Jebavya,b, Jan M. Horaceka,b
a Department of Military Internal Medicine and Military Hygiene, University of Defence, Faculty of Military Health Sciences, Hradec Kralove, Czech Republic
b 4th Department of Internal Medicine - Hematology, Faculty of Medicine in Hradec Kralove, Charles University in Prague and University Hospital Hradec Kralove, Czech Republic
c Department of Informatics and Quantitative Methods, , Faculty of Informatics and Management, University of Hradec Kralove, Czech Republic
d Institute of Clinical Biochemistry and Diagnostics, University Hospital Hradec Kralove, Czech Republic

Objectives: Acute myeloid leukemia (AML) cells are highly resistant to therapy. The presumed molecular basis of this resistance is the effect of tumor necrosis factor alpha (TNF-α) and other cytokines on endothelial adhesion molecule expression. The aim of this study was to test the hypothesis that cytokines and soluble adhesion molecules correlate in AML.

Methods: Baseline serum levels of 17 cytokines and 5 soluble adhesion molecules were measured in 53 AML patients using biochip array technology. Age, leukocyte count, secondary AML, CRP, FLT3-ITD and remission were variables. Statistical analysis was performed in R version 3.1.2.

Results: VCAM-1 correlated with ICAM-1 (P < 0.0001), E-selectin (P < 0.0001), leukocyte count (P = 0.0005) and TNF-α (P = 0.0035). E-selectin correlated with leukocyte count (P < 0.0001), P-selectin (P = 0.0032) and MCP-1 (P = 0.0119). CRP correlated with IL-6 (P < 0.0001), leukocyte count negatively correlated with IL-7 (P = 0.0318). FLT3-ITD was associated with higher E-selectin (P = 0.0010) and lower IL-7 (P = 0.0252). Secondary AML patients were older. Failure of induction therapy was associated with significantly higher CRP and lower P-selectin. Leukocyte count (P < 0.0001), FLT3-ITD (P = 0.0017) and secondary AML (P = 0.0439) influenced the principal component.

Conclusions: Leukemic cells can modulate the microenvironment. Cytokine, adhesion molecule levels and leukocyte count correlate in AML. Understanding these mechanisms may form the basis of novel therapeutic approaches.

Keywords: cytokines, adhesion molecules, acute myeloid leukemia, TNF-alpha, FLT3-ITD

Received: April 24, 2015; Accepted: July 10, 2015; Prepublished online: September 4, 2015; Published: March 30, 2016


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