PLASMA CYTOKINE AND ADHESION MOLECULE PROFILE IN PATIENTS TREATED FOR ACUTE MYELOID LEUKEMIA

Sborník

Background. Cytokines and adhesion molecules have been studied as markers of immune system activation in various diseases including hematological malignancies. Alterations in this network may have direct effect on the malignant cells or have indirect effect on leukemogenesis through altered functions of bone marrow stromal elements. The knowledge gained from multiple cytokine and adhesion molecule analysis should allow better diagnosis and disease management. Aims. The aim of our study was to evaluate plasma cytokine and adhesion molecule profile by biochip array technology in patients treated for acute myeloid leukemia (AML). Methods. A total of 15 AML patients (mean age 48.7 ± 12.1 years, median 51, 8 males and 7 females) treated with cyclic chemotherapy (3+7, 2+5, HiDAC) alone or in combination with high-dose chemotherapy (preparative regimen Bu/Cy2 or Cy/TBI) followed by autologous hematopoietic stem cell transplantation were studied. We evaluated plasma levels of the following 22 cytokines and adhesion molecules: interleukins (IL-1 alpha, IL-1 beta, IL-2, IL-3, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, IL-23), vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNFalpha), interferon-gamma (IFN-gamma), epidermal growth factor (EGF), monocyte chemotactic protein-1 (MCP-1), E-Selectin, L-Selectin, P-Selectin, Intercellular Adhesion Molecule-1 (ICAM-1), Vascular Cell Adhesion Molecule-1 (VCAM-1). All biomarkers were measured by biochip array technology on Evidence Investigator analyzer (Randox) at the diagnosis of AML (active leukemia) and at 6 months after completion of chemotherapy (durable complete remission /CR/ in all patients). Probability values (p) < 0.01 and lower were considered statistically significant. Results. Comparing plasma cytokine and adhesion molecule levels in active leukemia and in durable CR, we found significant increase in plasma IL-7 (5.34 ± 4.32 ng/L vs. 19.62 ± 12.05 ng/L; p < 0.001), EGF (16.48 ± 33.50 ng/L vs. 64.42 ± 35.33 ng/L; p < 0.001) and VEGF (63.93 ± 67.85 ng/L vs. 114.39 ± 54.90 ng/L; p < 0.01). On the other hand, we found significant decrease in plasma E-Selectin (30.19 ± 20.46 mcg/L vs. 12.99 ± 8.00 mcg/L; p<0.01). Plasma levels of other evaluated cytokines and adhesion molecules were without significant differences. Conclusions. Our results indicate that plasma levels of some cytokines and adhesion molecules (IL-7, EGF, VEGF, E-Selectin) are significantly altered in patients treated for AML, showing activity of the disease. Whether these alterations could serve as a prognostic marker for AML is not known. Further studies in a larger number of patients and comparing cytokine and adhesion molecule levels with established prognostic markers (cytogenetics, molecular genetics) will be needed to define the potential role of these and additional markers in the risk stratification of AML patients.The work was supported by research projects MO 0FVZ0000503 and MZO 00179906.

Haematologica, 2012; 97(s1):  16