EVALUATION OF SERUM LEVELS OF SELECTED CYTOKINES IN PATIENTS WITH NEWLY DIAGNOSED ACUTE LYMPHOBLASTIC LEUKEMIA USING BIOCHIP ARRAY TECHNOLOGY

ABSSUB-3080

Background: Cytokines have been studied as markers of immune system activation in various diseases including hematological malignancies. Alterations in this interacting functional 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 multi-analytical determination of cytokines could allow better diagnosis and management of hematological malignancies, since cytokines or their receptors may also represent a target for specific anticancer therapy at the molecular level. Recently, some studies reported the possible diagnostic and prognostic use of cytokine levels in newly diagnosed acute leukemias.

Aims: The aim of our study was to evaluate serum levels of selected cytokines in patients with newly diagnosed acute lymphoblastic leukemia (ALL) and in healthy subjects using the innovative biochip array technology. This approach allows simultaneous detection of multiple cytokines from a single sample.

Methods: Serum samples of 21 newly diagnosed ALL patients (median age 46, range 24 - 75 years, 17 males and 4 females, 20 B-ALL, 1 T-ALL) and 15 healthy subjects (median age 41, range 25 - 58 years, 11 males and 4 females) were analyzed. We evaluated serum levels of the following cytokines:  interleukin-5 (IL-5), interleukin-15 (IL-15), granulocyte macrophage colony stimulating factor (GM-CSF), macrophage inflammatory protein-1 alpha (MIP-1 alpha), soluble IL-2 receptor alpha (sIL-2R alpha), soluble IL-6 receptor (sIL-6R), soluble tumour necrosis factor receptor I (sTNFR-I), soluble tumour necrosis factor receptor II (sTNFR-II), matrix metalloproteinase-9 (MMP-9). All analytes were measured by biochip array technology using chemiluminescent sandwich immunoassays applied to the Evidence Investigator analyzer (Randox). Probability values (p) < 0.01 were considered statistically significant.

Results: In newly diagnosed ALL patients, we found significant increase in serum IL-15 (1.74 ± 0.97 ng/L vs. 0.81 ± 0.16 ng/L; p = 0.0008), MIP-1 alpha (6.36 ± 3.26 ng/L vs. 2.68 ± 1.47 ng/L; p = 0.0003), sIL-6R (2.29 ± 1.80 mcg/L vs. 0.89 ± 0.39 mcg/L; p = 0.006), sTNFR-I (0.96 ± 0.50 mcg/L vs. 0.25 ± 0.07 mcg/L; p = 0.000005), sTNFR-II (0.73 ± 0.51 mcg/L vs. 0.29 ± 0.14 mcg/L; p = 0.003). Serum levels of other evaluated cytokines were without significant differences.

Summary/Conclusion: Our results indicate that serum levels of some cytokines (IL-15, MIP-1 alpha, sIL-6R, sTNFR-I, sTNFR-II) are significantly altered in patients with newly diagnosed ALL, reflecting activity of the disease. Further investigation is needed to establish if the alterations observed in the levels of these molecules could be used as a prognostic indicator for ALL.

The work was supported by a long-term organization development plan 1011 (FMHS).

Keywords: Acute lymphoblastic leukemia, Cytokine

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