Serum Profile Of Multiple Cytokines and Adhesion Molecules In Newly Diagnosed AML Patients Differs In Those Who Did Not Reach Complete Remission After Anthracycline/Cytarabine Induction Therapy
Authors: Kupsa Tomas , Horacek Jan M , Vasatova Martina , Jebavy Ladislav , Zak Pavel 
Published: October 2019

Abstract

Background
Cytokines and adhesion molecules have been studied as markers of immune system activation in various diseases including AML/MDS. Cytokines are soluble molecules taking part in intercellular communication with a specific role in cell proliferation and differentiation control. 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 baseline serum levels of multiple cytokines and adhesion molecules in Caucasian population AML patients and compare it with standard prognostic indicators in patients with AML.

Methods
A total of 28 consecutive newly diagnosed AML patients (11 males, 17 females, age 21 to 71 years, mean 52.3 ± 12.1, median 55.4 years, 8 with better risk, 13 with intermediate risk, 7 with high risk according to cytogenetics and molecular genetics) were administered 3+7 induction regimen with escalated dose of daunorubicin 90mg/m2. 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 and compared with standard prognostic indicators in AML. Probability values (p) < 0.05 were considered statistically significant.

Results
As there was no significant difference between younger and elderly patients, we evaluated the cohort as a whole. Comparing serum cytokine and adhesion molecule levels in patients who did not achieve CR after induction therapy (n=6, 21.5%) to those who achieved CR (n=22, 78,5%) a statistically significant increase in serum IL-2 (5.42 ± 5.42 ng/L vs. 2.02 ± 1.84 ng/L; p < 0,05), IL-7 (11.71 ± 10.77 ng/L vs. 3.50 ± 1.51 ng/L; p < 0.05), IL-8 (241.9 ± 225.3 ng/L vs. 34.31 ± 25.47 ng/L; p < 0.005), IL-10 (7.74 ± 6.83 ng/L vs. 2.83± 2.68 ng/L; p < 0.05) was found. Both groups differed from healthy individuals in serum levels of IL-4, IL-6, IL-13, VCAM-1, ICAM-1, E-selectin and L-selectin. We found moderate inverse correlation between overall survival and levels of VCAM-1 and E-selectin. There was no significant difference in cytokines and adhesion molecules levels among established prognostic subgroups in AML.

Conclusions
The results in general are in agreement with outcome of our pilot trial. Compared with the other studies of cytokine levels in newly diagnosed AML, our data indicate different conclusions. IL-2, IL-4 and IL-10 were more likely to be higher in those who attained remission (Kornblau et al., Blood 2010). We did not find association between IL-6 and IL-10 levels and survival in our studied group (Correa et al, Cytokine 2013). On the other hand we documented inverse correlation between levels of some adhesion molecules and overall survival. Whether these alterations depend on the studied population is not known definitely. To assess their predictive value for patient outcome, further studies in a larger number of patients is necessary.

Acknowledgment
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).

Disclosures:
No relevant conflicts of interest to declare.