Dynamics of Gene Expression of Surface Receptors of Apoptosis in Primary Patients with B-CLL during Induction Treatment

Introduction. The study of the regulation of the expression of the genes of the external pathway of apoptosis in tumor cells in patients with B-CLL is an urgent task that allows optimizing therapy.

Objective: To study the external pathway of apoptosis of tumor cells in B-CLL treated with RFC.

Materials and methods. The study involved 10 patients with a newly diagnosed B-CLL 2-3 stage in Rai. Median age is 60 years. Patients received courses of PolychemotherapyRFC (rituximab + fludarabine + cyclophosphamide). The expression level of the main genes of the external pathway of apoptosis (DR3, DR4 / 5, FAS, TNFR2 and TRAIL) was determined by the RQ-PCR method. The parameter of the investigated parameters was determined before and after the course of PCT. Quantification of gene expression was performed with respect to the expression of the ABL gene taken as 100%. Statistical analysis of the results was carried out using STATISTICA10 software.

Results. After the induction treatment of RFC, the average expression level of the DR3 gene increased from 553.5% to 1037.3% (p <0.05). Activity DR4 / 5 after therapy was characterized by a tendency to decrease from 727.01% to 543.9% (p <0.05). FAS activity decreased from 6855.9% to 848.1% (p <0.05). The expression level of TNFR2 increased from 1597.4% to 9618.3% (p <0.05), and the expression level of the TRAIL gene increased from 5801.3% to 6417.2% (p <0.05). Such dynamics of the surface receptor apoptosis gene indices was accompanied by clinical improvement in all patients, determined by the level of tumor lymphocytes (a decrease in the average values from 128 thousand to 26.73 thousand) and a 50% decrease in the size of peripheral lymph nodes.

Conclusion. Thus, it is possible that DR3, TNRF2 and TRAIL are the most significant of the surface receptor apoptosis genes being studied, as the increase in their expression is correlated with the positive antitumor response. Reducing the level of expression of DR4 / 5 and FAS genes may indicate their lesser role in achieving a direct antitumor response.