medbioМедико-биологические проблемы жизнедеятельностиMedical and Biological Problems of Life Activity2074-2088Республиканский научно-практический центр радиационной медицины и экологии человекаmedbio-183Research ArticleОБЗОРЫ И ПРОБЛЕМНЫЕ СТАТЬИREVIEWS AND PROBLEM ARTICLESКлональная эволюция лейкозных клеток и химиорезистентностьClonal evolution of leukemia cells and chemoresistanceСвирновскийА. И.SvirnovskiA. .noemail@neicon.ruПасюковВ. В.PasiukovV. .noemail@neicon.ruКравченкоД. В.KravchenkoD. .noemail@neicon.ruФедуроН. Ф.FeduroN. .noemail@neicon.ruСергиевичО. В.SergievichO. .noemail@neicon.ruТарасИ. Б.TarasI. .noemail@neicon.ruСвирновскаяЭ. Л.SvirnovskayaE. .noemail@neicon.ruRepublican Research Center for Transfusiology and Medical Biotechnologies, Minsk, BelarusRussian FederationRepublican Research Center for Radiation Medicine and Human Ecology, Gomel, BelarusRussian Federation201702032023012428Copyright © Свирновский А.И., Пасюков В.В., Кравченко Д.В., Федуро Н.Ф., Сергиевич О.В., Тарас И.Б., Свирновская Э.Л., 20232023Свирновский А.И., Пасюков В.В., Кравченко Д.В., Федуро Н.Ф., Сергиевич О.В., Тарас И.Б., Свирновская Э.Л.Svirnovski A..., Pasiukov V..., Kravchenko D..., Feduro N..., Sergievich O..., Taras I..., Svirnovskaya E...Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://medbio.ejournal.by/jour/article/view/183

Лейкозные клетки накапливают мутации и эпигенетические изменения в процессе развития заболевания, формируя гетерогенные популяции клеток, которые являются объектом выбора для воздействия и могут по-разному реагировать на терапию. Химиотерапия, в свою очередь, воздействует на вновь образованные мутации ДНК и может уничтожать наиболее чувствительные к лекарственным препаратам лейкозные клетки, сохраняя химиоиндуцированные устойчивые субклоны. Поэтому необходимо следить за изменениями в субклональной структуре во время прогрессирования заболевания, так как нарастающая клональная эволюция лейкозных клеток является основной причиной лекарственной устойчивости и неэффективности лечения. Таргетная терапия базируется на учете молекулярного типа заболевания, тогда как цитотоксическая терапия - на определяемой клеточной химиочувствительности пациентов. Оценка клеточной чувствительности к лекарственным препаратам не является альтернативой определению минимальной остаточной болезни или полного секвенирования генома для выбора терапии. Так как нелегко ингибировать эволюцию генома опухоли, определение чувствительности клеток в процессе опухолевого роста может оказаться важным при индукции ремиссии. Тем не менее, преимущества отдельных процедур мониторинга не всегда очевидны.

Leukemic cells accumulate mutations and epigenetic changes in the process of disease development forming heterogeneous cell populations that are subject to selection and may respond differentially to therapy. Chemotherapy in turn damages new DNA generating mutations, and may kill leukemia cells most sensitive to drugs and select drug induced resistant subclones. Therefore, it is necessary to monitor changes in the subclonal composition during disease progression as such increased leukemia cell clonal evolution is the main reason for drug resistance and treatment insufficiency. Targeted treatment may be based on the molecular type of disease and on the tested cellular chemosensitivity of the individual patient at least for remission induction. Cellular drug sensitivity evaluation is not alternative to minimal residual disease estimation and whole exome sequencing. As it is not so easy to inhibit tumor evolution, diagnostics of cells sensitivity in the process of evolution may be of particular interest with remission induction. However, advantages of monitoring procedures sometimes are not so obvious.

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The authors declare that there are no conflicts of interest present.