DNA DOUBLE-STRANDED BREAKS AND REPAIRS IN ACUTE LEUKEMIA

Abstract

Relevance: Double-strand Relevance: Errors in the damage repair system, such as double-stranded DNA breaks, can lead to mutations that will be passed on to subsequent generations of cells, and some of these mutations may have oncogenic potential. The study aimed to evaluate the number of double-stranded breaks and DNA repairs of peripheral blood lymphocytes in a group of conditionally healthy children and in patients diagnosed with acute leukemia (AL) to develop a method for predicting the outcome of the disease and determining the effectiveness of therapy. Methods: peripheral blood lymphocytes were studied: a) 38 conditionally healthy children (control group); b) 100 patients diagnosed with acute leukemia (AL); c) 14 children with relapse of the disease. Double-stranded DNA breaks/repairs were examined using the Aklides system (MEDIPAN, Germany), consisting of a fluorescent analyzer and the AKLIDES Nuk software. Results: In patients with T-lymphoblastic leukemia, both at admission and the end of Day 7 at the hospital, the number of 53BPI repair foci was, on average, three times higher than the number of DNA damages. In most cases, the ratio of breaks/repairs indicators during treatment did not change among patients with B-line leukemia. Double-stranded DNA breaks prevailed over repairs, with the newly established disease on the 7th, 15th day, and 3rd month of treatment. Overall, 22 samples were tested using RT-PCR, and results were considered as follows:1 (4%) – positive, 13 (59%) – negative, 8 (37%) -– invalid. Conclusion: The level of lymphocyte DNA damage in patients with B-ALL was higher than expected. In addition, the ratio of double-strand breaks to repairs remained unchanged at all stages of therapy in patients with B-ALL. The changes we suggest in these patients can be observed during and/or after maintenance therapy. Monitoring double-strand breaks/reparations was the initial step in developing a method of predicting the disease outcome and determining the therapy efficacy. The results obtained are of direct interest and require further research.