bloodjourГематология и трансфузиологияRussian journal of hematology and transfusiology0234-57302411-3042ООО Издательский дом «Практика»10.35754/0234-5730-2025-70-1-27-39bloodjour-615Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESМутации в гене TP53 и цитогенетические нарушения в опухолевых клетках у больных первичной медиастинальной В-клеточной крупноклеточной лимфомойTP53 gene mutations and cytogenetic aberrations in tumor cells of patients with primary mediastinal B-cell large cell lymphomahttps://orcid.org/0000-0002-5522-7531МангасароваЯ. К.MangasarovaY. K.

Мангасарова Яна Константиновна, кандидат медицинских наук, заведующая отделением химиотерапии лимфатических опухолей с блоком трансплантации костного мозга и гемопоэтических стволовых клеток с  дневным стационаром

125167, г. Москва

Yiana K. Mangasarova, Cand. Sci. (Med.), head of the Department of Chemotherapy of Lymphatic tumors with Bone Marrow and Hematopoietic Stem Cell Transplantation Unit

125167, Moscow

mangasarova.y@blood.ruhttps://orcid.org/0000-0002-6253-3334БидерманБ. В.BidermanB. V.

Бидерман Белла Вениаминовна, кандидат биологических наук, старший научный сотрудник лаборатории молекулярной гематологии

125167, г. Москва

Bella V. Biderman, Cand. Sci. (Biol.), Senior Researcher, Laboratory of Molecular Hematology

125167, Moscow

bella_biderman@mail.ruhttps://orcid.org/0000-0003-1613-652XОбуховаТ. Н.ObukhovaT. N.

Обухова Татьяна Никифоровна, кандидат медицинских наук, заведующая лабораторией кариологии

125167, г. Москва

Tatiana N. Obukhova, Cand. Sci. (Med.), Head of the Karyology Laboratory

125167, Moscow

obukhova_t@mail.ruАбдурашидоваР. Р.AbdurashidovaR. R.

Абдурашидова Руниза Равильевна, гематолог отделения химиотерапии лимфатических опухолей с блоком трансплантации костного мозга и гемопоэтических стволовых клеток с дневным стационаром 

125167, г. Москва

Runiza R. Abdurashidova, hematologist of the Department of Lymphatic Tumors with Hematopoietic stem cell transplantation unit and day hospital

125167, Moscow

runiza.abdurashidova@yandex.ruhttps://orcid.org/0000-0003-3163-4930АбрамоваТ. В.AbramovaT. V.

Абрамова Татьяна Валерьевна, кандидат медицинских наук, научный сотрудник лаборатории генной инженерии

125167, г. Москва

Tatyana V. Abramova, Cand. Sci. (Med.), Research associate Laboratory of Genetic Engineering

125167, Moscow

abramova.blood@gmail.comhttps://orcid.org/0000-0003-4263-8275МагомедоваА. У.MagomedovaA. U.

Магомедова Аминат Умарасхабовна, доктор медицинских наук, ведущий научный сотрудник отделение химиотерапии лимфатических опухолей с блоком трансплантации костного мозга и гемопоэтических стволовых клеток с дневным стационаром

125167, г. Москва

Aminat U. Magomedova, Dr. Sci. (Med.), Leading Researcher of the Department of Lymphatic Tumors with a hematopoietic stem cell transplantation unit and a day hospital

125167, Moscow

maminat@mail.ruhttps://orcid.org/0000-0001-8044-598XЧабаеваЮ. А.ChabaevaYu. A.

Чабаева Юлия Александровна, кандидат технических наук, заместитель заведующего информационно-аналитическим отделом

125167, г. Москва

Yuliya A. Chabaeva, Cand. Sci. (Tech.), deputy Head of the information and analytical Department

125167, Moscow

uchabaeva@gmail.comhttps://orcid.org/0000-0001-5171-0414ГабееваН. Г.GabeevaN. G.

Габеева Нэлли Георгиевна, кандидат медицинских наук, гематолог отделения гематологии и химиотерапии лимфом с блоком трансплантации костного мозга и гемопоэтических стволовых клеток

125167, г. Москва

Nelli G. Gabeeva, Cand. Sci. (Med.), hematologist of the Department of Hematology and Chemotherapy of Lymphomas with Bone Marrow and Hematopoietic Stem Cell Transplantation Unit

125167, Moscow

dr.gabeeva@gmail.comhttps://orcid.org/0000-0002-2639-7419ЗвонковЕ. Е.ZvonkovE. E.

Евгений Евгеньевич Звонков, доктор медицинских наук, заведующий отделением гематологии и химиотерапии лимфом с блоком трансплантации костного мозга и гемопоэтических стволовых клеток

125167, г. Москва

Evgeny E. Zvonkov, Dr. Sci. (Med.), Head of the Department of Hematology and Chemotherapy of Lymphomas with Bone Marrow and Hematopoietic Stem Cell Transplantation Unit

125167, Moscow

dr.zvonkov@gmail.comhttps://orcid.org/0000-0001-9463-9187СудариковА. Б.SudarikovА. B.

Судариков Андрей Борисович, доктор биологических наук, заведующий лабораторией молекулярной гематологии

125167, г. Москва

Andrey B. Sudarikov, Dr. Sci. (Biol.), Head of Molecular Genetic Lab

125167, Moscow

dusha@blood.ruФГБУ «Национальный медицинский исследовательский центр гематологии» Министерства здравоохранения Российской ФедерацииРоссияNational Medical Research Center for HematologyRussian Federation2025130320257012739Copyright © Мангасарова Я.К., Бидерман Б.В., Обухова Т.Н., Абдурашидова Р.Р., Абрамова Т.В., Магомедова А.У., Чабаева Ю.А., Габеева Н.Г., Звонков Е.Е., Судариков А.Б., 20252025Мангасарова Я.К., Бидерман Б.В., Обухова Т.Н., Абдурашидова Р.Р., Абрамова Т.В., Магомедова А.У., Чабаева Ю.А., Габеева Н.Г., Звонков Е.Е., Судариков А.Б.Mangasarova Y.K., Biderman B.V., Obukhova T.N., Abdurashidova R.R., Abramova T.V., Magomedova A.U., Chabaeva Y.A., Gabeeva N.G., Zvonkov E.E., Sudarikov А.B.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.htjournal.ru/jour/article/view/615Введение

Введение. Мутации в гене TP53 и цитогенетические нарушения (MYC/8q24, BCL2/18q21, BCL6/3q27, del17p13 и комплексный кариотип) играют важную роль в прогнозировании и выборе терапии при многих лимфопролиферативных заболеваниях, однако их значение в патогенезе и прогнозе первичной медиастинальной В-клеточной крупноклеточной лимфомы (ПМВКЛ) мало изучено.

Цель — оценить частоту мутаций в гене ТР53 и цитогенетических нарушений (MYC/8q24, BCL2/18q21, BCL6/3q27, del17p13 и комплексный кариотип) и влияние этих нарушений на результаты лечения ПМВКЛ.

Материалы и методы

Материалы и методы. В исследование включен 51 больной, получивший терапию по ответ-адаптированному протоколу «DA-EPOCH-R» с 2012 по 2024 г. Выполнен анализ мутаций TP53 (экзоны 4–10) методом высокопроизводительного секвенирования (n = 31/51 (61 %)), флуоресцентная in situ гибридизация для выявления хромосомных нарушений с вовлечением локусов генов MYC/8q24, BCL2/18q21, BCL6/3q27 и del17p13 (n =31/51 (61 %)) и стандартное кариологическое исследование (n = 31/51 (61 %)). Из-за низкой митотической активности опухолевых клеток достаточное количество митозов было получено только в 16/31 (52 %) образцах ПМВКЛ.

Результаты

Результаты. Мутация TP53 выявлена у 4 (13 %) из 31 больного, у 3 из них найденные мутации классифицировали как патогенные. У 2 (6 %) из 31 больного были выявлены изолированные транслокации с участием локуса MYC/8q24 и BCL6/3q27. Структурные перестройки хромосомы 17 в локусе гена ТР53 и транслокации с участием локуса гена BCL2/18q21 не были выявлены ни в одном случае. Общая выживаемость в группах TP53-WT и TP53-MUT на сроке 36 мес. составила 85 % против 100 % соответственно (p = 0,61). Вероятность рецидивов/прогрессирования у больных с наличием TP53-MUT составила 33 %, а TP53-WT — 20 % (p = 0,35).

Заключение

Заключение. Исследуемые маркеры встречаются редко и не имеют прогностической значимости у больных ПМВКЛ. Необходимы исследования, направленные на идентификацию драйверных событий биологически дискретных подтипов В-клеточных агрессивных лимфом, выделение факторов риска для каждого из них, что будет служить основанием для прецизионной терапии.

Introduction

Introduction. TP53 gene mutations and cytogenetic abnormalities (MYC/8q24, BCL2/18q21, BCL6/3q27, del17p13, and complex karyotype) play an important role in prognosis and therapy selection for various lymphoproliferative diseases. However, their signifi cance in the pathogenesis and prognosis of primary mediastinal B-cell large cell lymphoma (PMBCL) remains poorly understood and warrants further investigation.

Aim

Aim: to assess the frequency of TP53 gene mutations and cytogenetic aberrations (MYC/8q24, BCL2/18q21, BCL6/3q27, del17p13, and complex karyotype) and their impact on treatment outcomes in PMBCL.

Materials and methods

Materials and methods. The study included 51 patients who underwent therapy using the response-adapted DA-EPOCHR protocol from 2012 to 2024. Analysis of TP53 mutations (exons 4–10) was performed using high-throughput sequencing (n = 31/51 (61 %)). FISH analysis was conducted to identify chromosomal abnormalities involving the loci of MYC/8q24, BCL2/18q21, BCL6/3q27, and del17p13 (n = 31/51 (61 %)), and standard karyotyping was carried out (n = 31/51 (61 %)). Due to the low mitotic activity of tumor cells, suffi cient mitoses were obtained in only 16/31 (52%) PMBCL samples.

Results

Results. TP53 mutations were identifi ed in 4/31 (13%) patients, with three of these mutations classifi ed as pathogenic. Isolated translocations involving MYC/8q24 and BCL6/3q27 loci were detected in 2/31 (6 %) patients. Structural rearrangements of chromosome 17 in the TP53 locus and translocations involving the BCL2/18q21 locus were not identifi ed in any case. At 36 months, overall survival in the TP53-WT and TP53-MUT groups was 85 % and 100 %, respectively (p = 0.61). The relapse/progression rate was 33 % in TP53-MUT patients and 20 % in TP53-WT patients (p = 0.35).

Conclusion

Conclusion. The fi ndings demonstrate the rarity and lack of prognostic signifi cance of the investigated markers in PMBCL patients. These results underscore the need for further research to identify driver events in biologically discrete subtypes of aggressive B-cell lymphomas, as well as risk factors specifi c to each subtype. Such research will provide a foundation for the development of precision therapy approaches.

первичная медиастинальная В-клеточная крупноклеточная лимфомаTP53MYC/8q24BCL2/18q21BCL6/3q27del17p13primary mediastinal B-cell large cell lymphomaTP53MYC/8q24BCL2/18q21BCL6/3q27del17p13исследование не имело спонсорской поддержки.the study had no financial support.ReferencesBlagih J., Buck M. D., Vousden K. H. p53, cancer and the immune response. Journal of Cell Science. 2020; 133(5): jcs237453. DOI: 10.1242/jcs.237453.Blagih J., Buck M. D., Vousden K. H. p53, cancer and the immune response. Journal of Cell Science. 2020; 133(5): jcs237453. DOI: 10.1242/jcs.237453.Chasov V., Mirgayazova R., Zmievskaya E., et al. Key Players in the Mutant p53 Team: Small Molecules, Gene Editing, Immunotherapy. Front. Oncol. 2020; 10: 1460. DOI: 10.3389/fonc.2020.01460.Chasov V., Mirgayazova R., Zmievskaya E., et al. Key Players in the Mutant p53 Team: Small Molecules, Gene Editing, Immunotherapy. Front. Oncol. 2020; 10: 1460. DOI: 10.3389/fonc.2020.01460.Döhner H., Stilgenbauer S., Benner A., et al. 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The authors declare that there are no conflicts of interest present.