Цитокиновый статус больных хроническим миелолейкозом

Abstract

Introduction. Altered cytokine secretion has been described in many types of cancer. Being a key mediator of intercellular interactions, they can contribute to the development of resistance to targeted therapy and cytostatic drugs in chronic myeloid leukemia (CML). Aim. To evaluate the relationship between cytokine spectrum indicators in patients with CML and the effectiveness of targeted tyrosine kinase inhibitors (TKI) therapy. Materials and methods. Quantitative determination of the concentration of cytokines TNF-α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-18, IFN-α in blood serum of patients with CML (n = 60) and apparently healthy blood donors (n = 22) was carried out using enzyme-linked immunosorbent assay (ELISA). The phase of the disease and the depth of molecular response were determined according to criteria of the European Leukemia Net 2020. Stratification of CML patients by risk groups was carried out according to the Sokal (1984), EUTOS long-term survival (ELTS) (2016) scores. Hematological and non-hematological toxicity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v.5.0, 2017). Results. It was found that the serum concentration of a number of cytokines in the group of patients with CML was significantly higher compared to the control group: TNF-α – 2.80 and 0.70 pg/ml, p < 0.001, IL-6 – 3.10 and 0.70 pg/ml, p < 0.001, IL-18 – 296.40 and 122.10 pg/ml, p < 0.001, IL-10 – 5.15 and 0.95 pg/ml, p < 0.001, IFN-α – 5.60 and 4.00 pg/ml, p = 0.006, respectively. Among patients with CML, the level of cytokines varied depending on the level of molecular response and the type of TKI. Patients who did not achieve a major molecular response (MMR) were characterized by a significantly greater increase in the secretion of TNF-α, IL-6 and IL-1β (6.65 and 2.30 pg/ml, p = 0.004, 9.40 and 2.80 pg/ml, p < 0.001, 3.69 and 0.88 pg/ml, p = 0.004, respectively) compared with patients with MMR. However, only IL-6 was a statistically significant prognostic factor influencing the achievement of MMR (odds ratio 1.131, confidence interval 1.015–1.260, p = 0.025). Among patients receiving imatinib therapy, the level of TNF-α was lower compared to patients receiving nilotinib, dasatinib and bozutinib (2.10, 4.00, 6.85 and 4.25 pg/ml, respectively, p = 0.013). Conclusion. The results of the research demonstrated increased secretion of TNF-α, IL-6, IL-18, IL-10, and IFN-α in CML patients, which may indicate an important role in the pathogenesis of CML. TNF-α, IL-6, and IL-1 levels were higher in patients who did not achieve MMR, and IL-6 was a statistically significant predictor the achievement of MMR.