Значение полиморфизмов генов TPMT, NUDT15 в метаболизме 6-меркаптопурина у больных острыми лимфобластными лейкозами/лимфомами

Введение. 6-меркаптопурин (6-МП) является одним из основных препаратов, применяемых для лечения больных острыми лимфобластными лейкозами/лимфомами (ОЛЛ/ЛБЛ). Степень проявлений нежелательных лекарственных реакций (НЛР) при лечении 6-МП значимо различается среди больных. Одной из причин индивидуальных различий является наличие однонуклеотидных полиморфизмов в  генах, кодирующих ключевые ферменты, участвующих в метаболизме 6-МП.

Цель — анализ литературы, посвященной изучению значения полиморфизмов генов TPMT и NUDT15 в метаболизме 6-МП у больных ОЛЛ/ЛБЛ.

Основные сведения. TPMT и NUDT15 — это гены, которые кодируют ферменты, участвующие в ключевых этапах метаболизма 6-МП. Вещества, которые образуются в  результате этих реакций, определяют терапевтические и  токсические свойства 6-МП. Изменение соотношений их концентраций приводит к  развитию НЛР. Гены TPMT и NUDT15 содержат ряд однонуклеотидных полиморфизмов, ассоциированных с различной активностью кодируемых ферментов. Комбинации этих аллельных вариантов определяют функциональный и нефункциональный фенотипы. У  носителей нефункционального варианта чаще отмечается развитие токсичности на  фоне терапии 6-МП, чем у носителей функционального варианта. У носителей нефункционального варианта TPMT или NUDT15 доза 6-МП, возможно, должна быть снижена с целью минимизации развития НЛР.

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