SERUM LEVELS OF MULTIPLE CYTOKINES AND ADHESION MOLECULES IN PATIENTS WITH NORMAL KARYOTYPE - ACUTE MYELOID LEUKEMIA

ABSSUB-4262

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. Alterations in this interacting functional network may have direct effect on the malignant cells or indirect effect on leukemogenesis through altered functions of bone marrow stromal elements. 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 and changes related to karyotype in patients treated for AML.

Methods: A total of 51 AML patients were studied. Two subgroups comprising 24 normal karyotype (CN-AML) and 27 aberrant karyotype AML patients were studied. These two subgroups did not differ in age (49.8 ± 12.3 vs. 55.3 ± 13.4 years), mean leukocyte count (44.8 ± 37.9 vs. 21.0 ± 25.7 x 1000/µL) or mean CRP (34.7 ± 37.2 vs. 32.4 ± 30.6 mg/L) of studied subjects. Further, in the group of CN-AML, we compared findings of patients having NPM 1 mutated (n=5) to patients with FLT3-ITD and NPM 1 mutated (n=8). Similarly, there was no difference in age (50.1 ± 14.5 vs. 49.8 ± 13.6 years), mean leukocyte count (62.46 ± 35.34 vs. 73.66 ± 73.36 x 1000/µL) or CRP levels (46.2 ± 34.6 vs. 43.0 ± 33.5 mg/L) between these two CN-AML subgroups.

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). Probability values (p) < 0.05 were considered statistically significant.

Results: Comparing serum cytokine and adhesion molecule levels, we found in CN-AML a significant increase in serum E-selectin (34.49 ± 18.23 mcg/L vs. 13.98 ± 9.11 mcg/L; p = 0.00018), L-selectin (2962.50 ± 706.20 mcg/L vs. 2187.12 ± 1060.01 mcg/L; p = 0.0092) and VCAM-1 (855.34 ± 386.02 ng/L vs. 600.73 ± 180.79 ng/L; p = 0.039). On the other hand the serum levels of IL-7 (3.12 ± 1.98 ng/L vs. 5.81 ± 3.66 ng/L; p = 0.029) and EGF (7.36 ± 7.06 ng/L vs. 21.08 ± 23.98 ng/L; p = 0.035) were significantly decreased.

The presence of FLT3-ITD in CN-AML with NPM 1 mutation was associated with higher IL-1 alpha (0.66 ± 0.16 ng/L vs. 0.20 ± 0.27 ng/L; p = 0.035), IL-4 (1.69 ± 0.89 ng/L vs. 0.34 ± 0.54 ng/L; p = 0.046), E-selectin (54.76 ± 16.32 mcg/L vs. 25.06 ± 7.61 mcg/L; p = 0.011) and P-selectin (206.21 ± 61.44 mcg/L vs. 106.72 ± 29.28 mcg/L; p = 0.037) levels.

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-1 alpha, IL-4, IL-7, EGF, E-, P-, L-selectin) are significantly altered in AML patients and may reflect activity of the disease based on cytogenetic and molecular genetic changes. Whether these alterations could serve as a prognostic marker for AML is not known. 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, Molecular cytogenetics

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