The Role of Tumor Necrosis Factor and ITS Soluble Receptors in Myelosuppression Developing in B-Cell Chronic Lymphocytic Leukemia

Introduction. Myelosuppression with severe anemia or thrombocytopenia refers to the adverse factors in clinical course of B-cell chronic lymphocytic leukemia (B-CLL). According to the existing data, in B-CLL patients (pts) the production of TNF and its soluble receptors, such as sTNFRI and sTNFRII, is broken. However, the final role of these proteins in myelosuppression developing in B-CLL pts is studied poorly. Purpose of the study. To determine the role of TNF, sTNFRI and sTNFRII in myelosuppression, developing in case of B-CLL. Materials and research methods. Determination of tumor necrosis factor (TNF) and its soluble receptors, such as sTNFRI and sTNFRII, was performed using blood plasma of 74 pts with B-CLL at different stages of the disease before treatment. Determining the concentration of TNF was carried out by the biological methods, using mouse fibroblasts cell culture line L929. The level of sTNFRI and sTNFRII was performed by immunological methods using the kits of BioSource Europe S. A., Belgium. These parameters were analyzed in relation with complete blood counts of the pts with B-CLL. The control group consisted of 15 healthy blood donors. Probability statistics was evaluated using Student's t-test. The relationship between the concentration of TNF, sTNFRІ, sTNFRІІ and haemograms of pts at different stages of B-CLL was established by the correlation coefficient (r), which was calculated by Excel program. Results of the investigation and their discussion. The significantly higher levels of TNF (0.938 ± 0.124 ng/ml) and sTNFRII (32.180 ± 4.350 ng/ml) in plasma of B-CLL pts at all stages of the disease compared to healthy donors (0.089 ± 0.017 and 4.170 ± 0.231 ng/ml, accordingly) were established. On the other hand, appreciably lower levels of TNF and sTNFRII in plasma of B-CLL pts at early stage in comparison with more advanced stages were determined. The concentrations of TNF and sTNFRII correlated negatively with hemoglobin level and red blood cell count, but positively with absolute lymphocytic count at the early stage of the disease. In addition, any changes were detected in TNF, sTNFRI and sTNFRII concentrations in patients with thrombocytopenia. Conclusions. These studies suggest that increasing of the concentration of TNF, sTNFRI and sTNFRII in case of B-CLL, as a result of their production by leukemic cell, may adversely affect hematopoiesis and induce development of anemia in pts with B-CLL. Thus there was installed a possible negative role of accumulated levels of TNF and sTNFRII in plasma of the pts with B-CLL in occurrence of bone marrow suppression at early stages of the disease. In advanced stages of B-CLL, the levels of the secreted TNF, sTNFRII may contribute to leukemic progression, which is confirmed by the high correlation between both indices. In addition, we didn't found significant changes in concentration of TNF, sTNFRI, sTNFRII in pts with varying content of platelets which pointed to the likely involvement of cytokines, other than TNF, sTNFRI, sTNFRII in the regulation of megakaryopoiesis in pts with B-CLL. So, determination of TNF and its soluble receptors may be used to predict the development of anemia as well as to initiate the treatment in B-CLL pts.