EVALUATION OF SERUM LEVELS OF MULTIPLE CYTOKINES AND ADHESION MOLECULES IN PATIENTS TREATED FOR ACUTE MYELOID LEUKEMIA

Background:

Acute myeloid leukemia (AML) shows a high degree of heterogeneity due to a variety of mutations and mechanisms involved in leukemogenesis. This heterogeneity is often not fully reflected in standard treatment approaches. Cytokines are soluble molecules that take part in intercellular communication, with a specific role in cell proliferation control. Postconsolidation immunotherapy with interleukin-2 and histamine dihydrochloride improved the leukemia-free survival of adult patients with acute myeloid leukemia in complete remission. Increased levels of soluble adhesion molecules have been shown to correlate with better outcome. Further 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 serum levels of multiple cytokines and adhesion molecules and changes related to disease activity in patients treated for AML.

Methods:

A total of 20 AML patients, mean age 53.5 ± 11.8 years, median 55.4, 7 males and 13 females, 4 with better risk, 7 with intermediate risk, 9 with high risk according to cytogenetics and molecular genetics, treated with cyclic chemotherapy (3+7, 2+5, HiDAC) alone or in combination with high-dose chemotherapy (FlAG-Ida, preparative regimen Bu/Flu/ATG) followed by allogeneic hematopoietic stem cell transplantation in 5 cases were studied. We evaluated serum 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-12, IL-13, IL-23), vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-alpha), 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 in durable complete remission (CR) at circa 6 months after completion of chemotherapy. Probability values (p) < 0.01 were considered statistically significant.

Results:

Comparing serum cytokine and adhesion molecule levels in active leukemia and in durable CR, we found significant increase in serum IL-7 (6.43 ± 4.91 ng/L vs. 21.36 ± 7.72 ng/L; p < 0.00005), EGF (17.52 ± 16.01 ng/L vs. 48.66 ± 28.15 ng/L; p < 0.0001) and VEGF (65.48 ± 41.33 ng/L vs. 158.92 ± 60.75 ng/L; p < 0.0005). On the other hand, we found significant decrease in serum L-selectin (2430.93 ± 1032.85 mcg/L vs. 1340.15 ± 308.27 mcg/L; p < 0.0005) and IL-13 (6.97 ± 3.41 ng/L vs. 4.02 ± 4.02 ng/L; p < 0.01). Serum levels of other evaluated cytokines and adhesion molecules were without significant differences.

Summary / Conclusion:

Our results indicate that serum levels of some cytokines and adhesion molecules (IL-7, EGF, VEGF, L-selectin, IL-13) are significantly altered in patients treated for AML, reflecting activity of the disease. Whether these alterations could serve as a prognostic marker for AML is not known. To assess their predictive value for patient outcome, further studies comparing cytokine and adhesion molecule levels with established prognostic markers (cytogenetics, molecular genetics) in a larger number of patients is necessary.

The work was supported by Specific research project “Analysis of defined prognostic factors in acute myeloid leukemia” (FMHS) and by a long-term organisation development plan 1011 (FMHS).

Email address: Tomas.Kupsa@seznam.cz

Abstrakta v časopise Haematologica 2013, Suppl1

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