M. Bulegenova ¹, A. Dunayeva ¹, S. Saliyeva ¹, A. Uskenbayeva ¹

1. «Scientific Center of Pediatrics and Pediatric Surgery» JSC, Almaty, the Republic of Kazakhstan

DOI: https://www.doi.org/10.52532/2521-6414-2023-2-68-22-27

UDC: 616.155.392-053.2-5:577.21

Year: 2023 issure: 68 number: 2 pages: 22-27

Download PDF:

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.
Keywords: double-stranded breaks, DNA repair, acute leukemia, lymphocytes, immunofluorescence.

List of sources used:

1. Основные пути репарации двойных разрывов ядерной геномной ДНК и взаимодействия между ними / Литвинов С.В. // Цитология и генетика. – 2014. – Т. 48, № 3. – С. 64-77 [Osnovnye puti reparacii dvojnyx razryvov yadernoj genomnoj DNK i vzaimodejstviya mezhdu nimi / Litvinov S.V. // Citologiya i genetika. – 2014. – T. 48, № 3. – S. 64-77 (in Russ.)] http://dspace.nbuv.gov.ua/bitstream/handle/123456789/126655/10-Litvinov.pdf?sequence=1
2. Bártova E., Legartová S., Dundr M., Suchánková J. A role of the 53BP1 protein in genome protection: structural and functional characteristics of 53BP1-dependent DNA repair // Aging (Albany NY). – 2019. – Vol. 11(8). – P. 2488-2511. https://doi.org/10.18632/aging.101917
3. Ермилова Т.И., Тарасова А.В., Шман Т.В. Анализ эффективности повреждения и репарации ДНК по выявлению фосфорилированной формы гистона γН2АХ в лейкемических клетках пациентов с острыми лейкозами «Гематология. Трансфузиология. Восточная Европа». – 2016. – №3(2). – С.330-343 [Ermilova T.I., Tarasova A.V., Shman T.V. Analiz e’ffektivnosti povrezhdeniya i reparacii DNK po vyyavleniyu fosforilirovannoj formy gistona γN2AX v lejkemicheskix kletkax pacientov s ostrymi lejkozami «Gematologiya. Transfuziologiya. Vostochnaya Evropa». – 2016. – №3(2).(in Russ.)]. https://oncology.by/assets/img/doc/sng-4.pdf
4. Palla V.V., Karaolanis G., Katafigiotis I., Anastasiou I., Patapis P., Dimitroulis D., Perrea D. gamma-H2AX: Can it be established as a classical cancer prognostic factor? // Tumour Biol. – 2017. – Vol. 39(3). – P. 31. https://doi.org/10.1177/1010428317695931
5. Булудова М.В., Полутов В.Э. Апоптоз: молекулярно-клеточные механизмы развития, значение в обеспечении клеточного гомеостаза // Бюллетень медицинских интернет-конференций. – 2017. – №6(7). – C. 1043-1045 [Buludova M.V., Polutov V.E. Apoptoz: molekulyarno-kletochnye mexanizmy razvitiya, znachenie v obespechenii kletochnogo gomeostaza // Byulleten’ medicinskix internet-konferencij, – 2017. – No. 6(7). – S. 1043-1045 (in Russ.)]. https://cyberleninka.ru/article/n/apoptoz-molekulyarno-kletochnye-mehanizmy-razvitiya-znachenie-v-obespechenii-kletochnogo-gomeostaza
6. Ray U., Raghavan S.C. Understanding the DNA double-strand break repair and its therapeutic implications // DNA Repair (Amst). – 2021. – Vol. 106. – P. 103177. https://doi.org/10.1016/j.dnarep.2021.103177;
7. Teachey DT, Pui CH. Comparative features and outcomes between paediatric T-cell and B-cell acute lymphoblastic leukaemia. Lancet Oncol. 2019 Mar;20(3):e142-e154. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9233195/;
8. Elitzur S., Izraeli Sh., Ben-Yehuda D., Gatt M.E. 77 – Lymphoid Leukemias // In: Clinical Immunology. – Sixth Edition. – Elsevier. – 2023. – P. 984-999. https://doi.org/10.1016/B978-0-7020-8165-1.00077-0
9. Bernstein C., Prasad A.R., Nfonsam V., Bernstein H. DNA Damage, DNA Repair and Cancer // In: New Research Directions in DNA Repair / ed. C. Chen. https://doi.org/10.5772/53919.
10. Alhegaili A.S. Role of DNA Repair Deficiency in Cancer Development // Pakistan J. Biol. Sci. – 2023. – Vol. 26. – P. 15-22. https://doi.org/10.3923/pjbs.2023.15.22
11. Broustas C.G., Lieberman HB. DNA damage response genes and the development of cancer metastasis // Radiat Res. – 2014. – Vol. 181(2). – P. 111-130. https://doi.org/10.1667/RR13515.1
12. Trenner A., Sartori A.A. Harnessing DNA Double-Strand Break Repair for Cancer Treatment // Front. Oncol. – 2019. – Vol. 9. – P. 1388. https://doi.org/10.3389/fonc.2019.01388;
13. Аклеев А.В., Пушкарёв С.А. Роль апоптоза и репарации ДНК в формировании адаптивного ответа у лиц, подвергшихся хроническому радиационному воздействию // Вестник ЮУрГГПУ. – 2008. – №11 [Akleev A.V., Pushkaryov S.A. Rol’ apoptoza i reparacii DNK v formirovanii adaptivnogo otveta u lic, podvergshixsya xronicheskomu radiacionnomu vozdejstviyu // Vestnik YuUrGGPU. – 2008. – №11. – С.273-276 (in Russ.)]. https://cyberleninka.ru/article/n/rol-apoptoza-i-reparatsii-dnk-v-formirovanii-adaptivnogo-otveta-u-lits-podvergshihsya-hronicheskomu-radiatsionnomu-vozdeystviyu