bloodjourГематология и трансфузиологияRussian journal of hematology and transfusiology0234-57302411-3042ООО Издательский дом «Практика»10.35754/0234-5730-2025-70-1-8-26bloodjour-606Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESОпределение мутаций FLT3 и мониторинг минимальной остаточной болезни при FLT3-позитивном остром миелоидном лейкозеDetermination of FLT3 mutations and minimal residual deasease monitoring in FLT3-positive acute myeloid leukemiahttps://orcid.org/0000-0003-1936-0084СидороваЮ. В.SidorovaY. V.

Сидорова Юлия Владимировна, кандидат медицинских наук, старший научный сотрудник лаборатории молекулярной гематологии

125167, г. Москва

Yulia V. Sidorova, Cand. Sci. (Med.), Senior Researcher, Laboratory of Molecular Hematology

125167, Moscow

sidorova.y@blood.ruhttps://orcid.org/0000-0002-7036-9968СеверинаН. А.SeverinaN. A.

Северина Наталия Александровна, кандидат биологических наук, старший научный сотрудник лаборатории молекулярной гематологии

125167, г. Москва

Nataliya A. Severina, Cand. Sci. (Biol.), Senior Researcher, Laboratory of Molecular Hematology

125167, Moscow

severina.n@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

biderman.b@blood.ruhttps://orcid.org/0000-0003-2957-1619РисинскаяН. В.RisinskayaN. V.

Рисинская Наталья Владимировна, кандидат биологических наук, старший научный сотрудник лаборатории молекулярной гематологии

125167, г. Москва

Natalya V. Risinskaya, Cand. Sci. (Biol.), Senior Researcher, Laboratory of Molecular Hematology

125167, Moscow

risinskaya.n@blood.ruhttps://orcid.org/0000-0002-8763-246XФевралеваИ. С.FevralevaI. S.

Февралева Ирина Серафимовна, кандидат биологических наук, ведущий научный сотрудник лаборатории молекулярной гематологии

125167, г. Москва

Irina S. Fevraleva, Cand. Sci. (Biol.), Leading Researcher, Laboratory of Molecular Hematology

125167, Moscow

fevraleva.i@blood.ruhttps://orcid.org/0009-0005-2774-1938КостроминаМ. А.KostrominaM. A.

Костромина Мария Александровна, студентка факультета фундаментальной медицины

119991, г. Москва

Maria A. Kostromina, student

119991, Moscow

mariya.kostromina.01@mail.ruСтародубС. М.StarodubS. М.

Стародуб София Михайловна, студентка института цифрового биодизайна и моделирования живых систем

119048, г. Москва

Sofia M. Starodub, 6th year student

119048, Moscow

starodub.sofi@mail.ruhttps://orcid.org/0000-0002-3548-8929КашлаковаА. И.KashlakovaA. I.

Кашлакова Анастасия Игоревна, гематолог отделения химиотерапии гемобластозов и депрессий кроветворения с блоком трансплантации костного мозга и гемопоэтических стволовых клеток

125167, г. Москва

Anastasia I. Kashlakova, Hematologist, Department of Chemotherapy of Hemoblastosis and Hematopoietic Depressions with Bone marrow and Hematopoietic Stem Cell Transplantation Unit

125167, Moscow

kashlakova.a@blood.ruhttps://orcid.org/0000-0002-8337-2242ЛукьяноваИ. А.LukyanovaI. A.

Лукьянова Ирина Анатольевна, кандидат медицинских наук, заведующая отделением дневного стационара онкологии и химиотерапии гемобластозов и депрессий кроветворения

125167, г. Москва

Irina A. Lukianova, Cand. Sci. (Med.), Hematologist, Head of the Department of Chemotherapy of Hemoblastosis and Hematopoietic Depressions with а Day In-patient Facility

125167, Moscow

lukyanova.i@blood.ruhttps://orcid.org/0000-0001-9463-9187СудариковА. Б.SudarikovA. B.

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

125167, г. Москва

Andrey B. Sudarikov, Dr. Sci. (Biol.), Head of the Laboratory of Molecular Hematology

125167, Moscow

sudarikov.a@blood.ruhttps://orcid.org/0000-0001-6177-3566ПаровичниковаЕ. Н.ParovichnikovaE. N.

Паровичникова Елена Николаевна, доктор медицинских наук, генеральный директор

125167, г. Москва

Elena N. Parovichnikova, Dr. Sci. (Med.), CEO

125167, Moscow

parovichnikova.e@blood.ruФГБУ «Национальный медицинский исследовательский центр гематологии» Министерства здравоохранения Российской ФедерацииРоссияNational Medical Research Center for HematologyRussian FederationФакультет фундаментальной медицины ФГБОУ ВО «Московский государственный университет им. М. В. Ломоносова»РоссияFaculty of Fundamental Medicine, M.V. Lomonosov Moscow State UniversityRussian FederationФГАОУ ВО «Первый Московский государственный медицинский университет им. И. М. Сеченова» Министерства здравоохранения Российской Федерации (Сеченовский Университет)РоссияI.M. Sechenov First Moscow State Medical University (Sechenov University)Russian Federation202512032025701826Copyright © Сидорова Ю.В., Северина Н.А., Бидерман Б.В., Рисинская Н.В., Февралева И.С., Костромина М.А., Стародуб С.М., Кашлакова А.И., Лукьянова И.А., Судариков А.Б., Паровичникова Е.Н., 20252025Сидорова Ю.В., Северина Н.А., Бидерман Б.В., Рисинская Н.В., Февралева И.С., Костромина М.А., Стародуб С.М., Кашлакова А.И., Лукьянова И.А., Судариков А.Б., Паровичникова Е.Н.Sidorova Y.V., Severina N.A., Biderman B.V., Risinskaya N.V., Fevraleva I.S., Kostromina M.A., Starodub S.М., Kashlakova A.I., Lukyanova I.A., Sudarikov A.B., Parovichnikova E.N.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/606Введение

Введение. Определение мутаций в гене FMS-подобной тирозинкиназы 3 (FLT3) играет важную роль в диагностике, определении прогноза и тактики терапии острого миелоидного лейкоза (ОМЛ).

Цель

Цель: сравнить основные методы, применяемые при диагностике мутаций FLT3 у больных ОМЛ.

Материалы и методы

Материалы и методы. Молекулярно-генетическую диагностику мутаций FLT3 проводили методами полимеразной цепной реакции (ПЦР) с фрагментным анализом (ПЦР-ФА), ПЦР-ФА с двойной меткой, методом тандемной дупликации (ТД-ПЦР), высокопроизводительного секвенирования (ВПС), аллель-специфичной ПЦР (АС-ПЦР) у больных ОМЛ, у которых устанавливали диагноз ОМЛ или которые наблюдались в ФГБУ «НМИЦ гематологии» Минздрава России с 2017 г. по 01.06.2024.

Результаты

Результаты. С помощью метода ПЦР-ФА были получены надежные результат выявления внутренних тандемных дупликаций гена FLT3 (FLT3-ITD). Метод ПЦР-ФА с двойной меткой обладает большей чувствительностью и специфичностью, что позволяет выявить FLT3-ITD у большего числа больных. ТД-ПЦР применим для определения минимальной остаточной болезни (МОБ) у части больных. ВПС не только позволяет получить информацию о месте вставки ITD и ее нуклеотидном составе, но также расширяет представления о точечных мутациях в первом и втором тирозинкиназных (TKD1 и TKD2) доменах, которые могут служить причиной резистентности к ингибиторам тирозинкиназ.

Заключение

Заключение. Применение нескольких методов для исследования мутаций FLT3 позволяет лучше идентифицировать минорные клоны FLT3-ITD, определять МОБ и точечные соматические мутации в TKD1 и TKD2 доменах. Даны рекомендации по молекулярно-генетической диагностике мутаций FLT3 при ОМЛ.

Introduction

Introduction. The identification of mutations in the FLT3 gene is essential for the diagnosis, prognosis, and selection of treatment strategies for acute myeloid leukemia (AML).

Aim

Aim: to compare the main methods used in the diagnosis of FLT3 mutations in patients with AML.

Materials and methods

Materials and methods. Identification of FLT3 gene mutations was carried out using polymerase chain reaction (PCR) with fragment analysis (PCR-FA), double-label PCR-FA, tandem duplication method (TD-PCR), next-generation sequencing (NGS), and allele-specific PCR (AS-PCR) in patients who were diagnosed or observed with AML at the National Medical Research Center for Hematology from 2017 to 01.06.2024.

Results

Results. The PCR-FA method showed reliable results in the testing of internal tandem duplications of FLT3 gene (FLT3-ITD). The double-label PCR-FA method had greater sensitivity and specificity that allowed detection of FLT3-ITD in a larger number of patients. TD-PCR was useful for determining minimal residual disease (MRD) in some patients. NGS provided information about the site of ITD insertion and its nucleotide composition, but also expanded our understanding of point mutations in the first and second tyrosine kinase (TKD1 and TKD2) domains, which may cause resistance to tyrosine kinase inhibitors.

Conclusion

Conclusion. The use of several methods to analyze FLT3 mutations makes it possible to make a more accurate identification of minor FLT3-ITD clones, as well as the detection of MRD and somatic point mutations within the TKD1 and TKD2 domains. Recommendations are given on the molecular genetic diagnosis of FLT3 mutations in AML.

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