Pediatric Hematology/Oncology and ImmunopathologyPediatric Hematology/Oncology and ImmunopathologyВопросы гематологии/онкологии и иммунопатологии в педиатрии1726-17082414-9314Fund Doctors, Innovations, Science for Children95110.24287/1726-1708-2025-24-1-188-198LITERATURE REVIEWОБЗОР ЛИТЕРАТУРЫFLT3 internal tandem duplications in acute myeloid leukemia: mechanism of formation and clinical significanceВнутренние тандемные дупликации в гене FLT3 при остром миелоидном лейкозе: механизм образования и клиническое значениеhttps://orcid.org/0000-0003-0098-919XItovA. B.ИтовА. Б.
Russian Federation

Albert B. Itov - MD in Clinical Laboratory Medicine of the Laboratory of Cytogenetics and Molecular Genetics.

1 Samory Mashela St., 117997, Moscow

Итов Альберт Баширович - врач клинической лабораторной диагностики лаборатории цитогенетики и молекулярной генетики.

117997, Москва, ул. Саморы Машела, 1

albertitov03@gmail.comhttps://orcid.org/0000-0002-2352-7716OlshanskayaYu. V.ОльшанскаяЮ. В.
Russian Federation

Moscow

Юлия Вячеславовна Ольшанская

Москва

Yuliya.Olshanskaya@dgoi.ruThe Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian FederationФГБУ «Национальный медицинский исследовательский центр детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева» Минздрава РоссииThe N.I. Pirogov Russian National Research Medical University of Ministry of Healthcare of the Russian FederationФГАОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России080420252411881982901202525022025Copyright ©; 2025, «D. Rogachev NMRCPHOI»Copyright ©; 2025, ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава России2025«D. Rogachev NMRCPHOI»ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава Россииhttps://creativecommons.org/licenses/by/4.0https://hemoncim.com/jour/article/view/951

This review presents the FLT3 gene structure and the working principle of the FLT3 protein coded by the gene, details the molecular mechanisms of FLT3 internal tandem duplication formation, the detailed structure and localization of tandem duplications in the FLT3 gene. Modern methods of FLT3-ITD diagnosis are described: fragment analysis, which provides an opportunity to estimate the allelic ratio, and next-generation sequencing, which allows for the study of the character of duplicated fragments and the localization of tandem duplications. This work presents the results of recent studies on the clinical significance of FLT3-ITD in acute myeloid leukemia with a normal karyotype and in the combination of FLT3-ITD with recurrent cytogenetic aberrations, as well as the results of studies showing the influence of the character of duplicated fragments and the location of FLT3-ITD insertion on survival rates. The main types of FLT3-inhibitors, their mechanism of action and clinical efficacy are described. Modern possibilities of FLT3-ITD monitoring and its practical significance for predicting the outcome of acute myeloid leukemia are presented.

В настоящем обзоре показаны строение гена FLT3 и принцип работы кодируемого геном белка FLT3, детализированы молекулярные механизмы образования внутренних тандемных дупликаций в гене FLT3 (FLT3-ITD), а также представлены подробная структура и локализация тандемных повторов в гене FLT3. Кроме того, описаны современные методы диагностики FLT3-ITD: фрагментный анализ, который дает возможность оценить аллельную нагрузку, и высокопроизводительное секвенирование, позволяющее изучить характер дуплицированных фрагментов и локализацию тандемных повторов. В статье представлены данные последних работ, посвященных клиническому значению FLT3-ITD при остром миелоидном лейкозе с нормальным кариотипом и при сочетании FLT3-ITD с рекуррентными цитогенетическими аберрациями, а также изложены результаты исследований, показывающие влияние характера дуплицированных фрагментов и места вставки FLT3-ITD на показатели выживаемости. Описаны основные типы FLT3-ингибиторов, механизм их действия и клиническая эффективность. Представлены современные возможности мониторинга FLT3-ITD и его практическая значимость для прогнозирования исхода острого миелоидного лейкоза. 

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