Определение мутаций FLT3 и мониторинг минимальной остаточной болезни при FLT3-позитивном остром миелоидном лейкозе

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

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. 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. 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.

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