OncohematologyOncohematologyОнкогематология1818-83462413-4023Publishing House ABV Press92110.17650/1818-8346-2024-19-2-26-33NEW DIRECTIONS, DIAGNOSTIC OPPORTUNITIES, AND TREATMENT ADVANCESНОВЫЕ НАПРАВЛЕНИЯ, ВОЗМОЖНОСТИ ДИАГНОСТИКИ И УСПЕХИ ЛЕЧЕНИЯGenetic polymorphisms as predictors of methotrexate toxicity: literature reviewГенетические полиморфизмы как предикторы токсичности метотрексата: обзор литературыhttps://orcid.org/0009-0008-8297-3629RadzhabovaG. A.РаджабоваГ. А.
Russian Federation

Build. 1, 8 Trubetskaya St., Moscow 119991

119991 Москва, ул. Трубецкая, 8, стр. 2

https://orcid.org/0000-0002-1469-2365ValievT. T.ВалиевТ. Т.
Russian Federation

Timur T. Valiev.

Build. 1, 8 Trubetskaya St., Moscow 119991; 24 Kashirskoe Shosse, Moscow 115522

Валиев Тимур Теймуразович.

119991 Москва, ул. Трубецкая, 8, стр. 2; 115522 Москва, Каширское шоссе, 24

timurvaliev@mail.ruhttps://orcid.org/0000-0001-8443-8816RyabukhinaYu. E.РябухинаЮ. Е.
Russian Federation

111 1st Uspenskoe Shosse, Lapino, Moscow region 143081

143081 Московская обл., д. Лапино, 1-е Успенское шоссе, 111

https://orcid.org/0000-0002-2373-2250SavelyevaM. I.СавельеваМ. И.
Russian Federation

5 Revolyutsionnaya St., Yaroslavl 150000

150000 Ярославль, ул. Революционная, 5

https://orcid.org/0000-0001-9001-1499AbdullaevSh. P.АбдуллаевШ. П.
Russian Federation

Build. 1, 2/1 Barrikadnaya St., Moscow 125993

125993 Москва, ул. Баррикадная, 2/1, стр. 1

https://orcid.org/0000-0002-0050-0721GurievaO. D.ГурьеваО. Д.
Russian Federation

24 Kashirskoe Shosse, Moscow 115522

115522 Москва, Каширское шоссе, 24

https://orcid.org/0000-0003-1564-424XZeynalovaP. A.ЗейналоваП. А.
Russian Federation

Build. 1, 8 Trubetskaya St., Moscow 119991; 111 1st Uspenskoe Shosse, Lapino, Moscow region 143081

119991 Москва, ул. Трубецкая, 8, стр. 2; 143081 Московская обл., д. Лапино, 1-е Успенское шоссе, 111

I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University)ФГАОУ ВО Первый Московский государственный медицинский университет им. И.М. Сеченова Минздрава России (Сеченовский Университет)N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of RussiaФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава РоссииClinical Hospital “Lapino” of the “Mother and Child” Group of companiesКлинический госпиталь «Лапино» группы компаний «Мать и дитя»Yaroslavl State Medical University, Ministry of Health of RussiaФГБОУ ВО «Ярославский государственный медицинский университет» Минздрава РоссииRussian Medical Academy of Continuing Professional Education, Ministry of Health of RussiaФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России0304202419226331301202402042024https://oncohematology.abvpress.ru/ongm/article/view/921

Background. A significant advancement in the treatment of high-grade aggressive non-Hodgkin’s lymphomas and acute lymphoblastic leukemia is the inclusion of high-dose (1000–5000 mg/m2) methotrexate in the treatment protocol. This approach has significantly increased the long-term survival rate, but it has been associated with toxicity, requiring supportive care. Factors that predict toxicity were identified, including genes involved in the metabolism (MTHFR) or transport (SLCO1B1) of methotrexate. The analysis of methotrexate metabolism has identified additional genes responsible for the elimination of this drug, allowing for more effective prevention and treatment of methotrexate-associated toxicity.

Aim. To study the genetic polymorphisms of enzymes involved in the methotrexate metabolism and associated toxicity in the treatment of pediatric acute lymphoblastic leukemia and non-Hodgkin’s lymphomas.

Materials and methods. Data were analyzed in specialized medical databases such as Pubmed, Scopus, Web of Science, Frontiers, and Google Scholar from 2001 to 2024.

Results. The main predictors of high-dose methotrexate-associated toxicity are gene polymorphisms in MTHFR, SLCO1B1, ARID5B.

Conclusion. Despite the contradictory data presented in the literature, it is important to consider the detection of polymorphisms during high-dose methotrexate treatment in order to administer timely supportive care and prevent significant toxicity.

Введение. Большим достижением в лечении высокоагрессивных неходжкинских лимфом и острого лимфобластного лейкоза стало включение в протоколы терапии высокодозного (1000–5000 мг/м2) метотрексата. Подобный подход позволил существенно повысить показатели многолетней выживаемости больных, но оказался сопряжен с токсичностью лечения, требующей проведения сопроводительной терапии. Поиск факторов, которые могли бы предопределить развитие токсичности, позволил выделить гены, участвующие в метаболизме (например, MTHFR) или транспорте (SLCO1B1) метотрексата. Дальнейший анализ метаболизма метотрексата, определение дополнительных генов, участвующих в элиминации этого препарата, позволят более эффективно профилактировать и лечить токсические осложнения, сопряженные с противоопухолевыми эффектами метотрексата.

Цель исследования – изучение генетических полиморфизмов ферментов, участвующих в метаболизме метотрексата, и ассоциированной с ними токсичности при лечении острого лимфобластного лейкоза и неходжкинских лимфом у детей.

Материалы и методы. Проведен анализ данных в специализированных медицинских базах PubMed, Scopus, Web of Science, Frontiers, Google Scholar с 2001 по 2024 г. Результаты. Основными предикторами токсичности при использовании высокодозного метотрексата являются полиморфизмы генов MTHFR, SLCO1B1 и ARID5B.

Заключение. Несмотря на противоречивые данные, представленные в литературе, следует принимать во внимание обнаруживаемые полиморфизмы при проведении лечения высокодозным метотрексатом и своевременно выполнять сопроводительную терапию, направленную на предотвращение выраженной токсичности.

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