SECONDARY ACUTE MYELOID LEUKEMIA PATIENTS DIFFER IN LEVELS OF INTERLEUKIN-7 AND EPIDERMAL GROWTH FACTOR FROM PRIMARY AML

ABSSUB-4251

Background: Acute myeloid leukemia (AML) shows a high degree of heterogeneity due to a variety of mutations and mechanisms involved in leukemogenesis. Cytokines are soluble molecules that take part in intercellular communication, with a specific role in cell proliferation control. Alterations in adhesion molecule network have been shown to impact prognosis of AML patients. We aimed to provide more evidence about baseline changes in cytokine and adhesion molecule profile related to age and AML origin. Further knowledge gained from multiple cytokine and adhesion molecule analysis should allow better diagnosis and disease management.

Aims: Evaluate differences in cytokine and adhesion molecule profile between primary and secondary AML.

Methods: A total of 47 newly diagnosed AML patients, mean age 52.1 ± 13.3, median 54.9 years, 18 males and 29 females, were studied. These patients were divided according to AML origin (primary vs. secondary AML, n=35 vs. 12). All cases of secondary AML had history of MDS. 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. Probability values (p) < 0.05 were considered statistically significant.

Results: The patients with AML of secondary origin had higher levels of IL-7 (8.68 ± 7.07 ng/L vs. 3.66 ± 2.02 ng/L; p = 0.021) and EGF (22.92 ± 21.90 ng/L vs. 8.46 ± 9.03 ng/L; p = 0.016) and higher age (63.3 ± 5.6 vs. 48.2 ± 14.0 years, p = 0.003).

Due to higher age in the secondary AML subgroup, we analysed age-related changes in  cytokine and adhesion molecule levels in patients without previous history of MDS. The primary AML patients of age 65 years and higher had significantly decreased serum levels of IL-12 (1.41 ± 1.32 ng/L vs. 4.51 ± 3.87 ng/L; p = 0.034) and IL-13 (2.14 ± 3.19 ng/L vs. 5.55 ± 4.02 ng/L; p = 0.034) compared to younger individuals, but IL-7 and EGF levels have not been significantly altered. Serum levels of other evaluated cytokines and adhesion molecules were without significant differences.

Summary/Conclusion: Our results indicate that serum levels of IL-7 and EGF are elevated in AML originating from MDS. Elevated levels of EGF trigger upregulation in MAPK/ERK pathway. This alteration might be associated with disease aggressiveness and might be of future therapeutic importance. The role of IL-7 in the pathogenesis is not clear at the moment. To assess their predictive value for patient outcome, further studies in a larger number of patients are 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).

Keywords: Adhesion, AML, Cytokine

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