EVI1 -позитивные лейкозы и миелодиспластические синдромы: теоретические и клинические аспекты (обзор литературы)

Н.Н. Мамаев, А.И. Шакирова, Е.В. Морозова, Т.Л. Гиндина

НИИ детской онкологии, гематологии и трансплантологии им. Р.М. Горбачевой, ФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова» Минздрава России, ул. Льва Толстого, д. 6/8, Санкт-Петербург, Российская Федерация, 197022

Для переписки: Николай Николаевич Мамаев, д-р мед. наук, профессор, ул. Льва Толстого, д. 6/8, Санкт-Петербург, Российская Федерация, 197022; e-mail: nikmamaev524@gmail.com

Для цитирования: Мамаев Н.Н., Шакирова А.И., Морозова Е.В., Гиндина Т.Л. EVI1-позитивные лейкозы и миелодиспластические синдромы: теоретические и клинические аспекты (обзор литературы). Клиническая онкогематология. 2021;14(1):103–17.

DOI: 10.21320/2500-2139-2021-14-1-103-117


РЕФЕРАТ

Настоящий обзор посвящен анализу теоретической базы и проводимой в клинике НИИ детской онкологии, гематологии и трансплантологии им. Р.М. Горбачевой терапии наиболее неблагоприятных в прогностическом отношении EVI1-позитивных вариантов миелоидных лейкозов и миелодиспластических синдромов. Основной акцент в работе сделан на доказательстве ведущей роли гена EVI1 в нарушении эпигенетической регуляции гемопоэза и, следовательно, целесообразности использования трансплантации аллогенных гемопоэтических стволовых клеток с гипометилирующими агентами и/или транс-ретиноевой кислотой для лечения этих заболеваний.

Ключевые слова: EVI1, острые миелоидные лейкозы, хронический миелоидный лейкоз, миелодиспластический синдром, аллоТГСК, гипометилирующие агенты, транс-ретиноевая кислота.

Получено: 12 сентября 2020 г.

Принято в печать: 6 декабря 2020 г.

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Статистика Plumx русский

ЛИТЕРАТУРА

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Влияние молекулярно-генетических и цитогенетических факторов на эффективность аллогенной трансплантации костного мозга у больных хроническим миелолейкозом

А.В. Горбунова, Т.Л. Гиндина, Е.В. Морозова, И.М. Бархатов, Н.Н. Мамаев, Б.В. Афанасьев

Институт детской онкологии, гематологии и трансплантологии им. Р.М. Горбачевой СПбГМУ им. акад. И.П. Павлова, Санкт-Петербург, Российская Федерация


РЕФЕРАТ

Известно, что развитие резистентности к терапии ингибиторами тирозинкиназ (ИТК) у пациентов с хроническим миелолейкозом (ХМЛ) и прогрессирование заболевания связаны с различными молекулярно-биологическими и цитогенетическими факторами, в т. ч. появлением мутаций в киназном домене гена BCR-ABL, изменением в характере экспрессии генов BCR-ABL и EVI1, наличием дополнительных хромосомных нарушений. В данном ретроспективном исследовании оценено влияние этих факторов на эффективность аллогенной трансплантации гемопоэтических стволовых клеток (аллоТГСК) у 35 больных ХМЛ с резистентностью к терапии ИТК. Показано, что наличие дополнительных хромосомных нарушений снижает частоту достижения полного молекулярного ответа после аллоТГСК. В отношении безрецидивной выживаемости неблагоприятным фактором прогноза служит высокий уровень экспрессии гена EVI1. Наличие мутаций в киназном домене гена BCR-ABL, связанных с резистентностью к ИТК, не оказывало влияния на общую и безрецидивную выживаемость, а также на частоту достижения полного молекулярного ответа в данной группе пациентов. В итоге у 9 из 10 пациентов, имевших мутацию T315I, был получен полный молекулярный ответ. Дополнительная стратификация пациентов в посттрансплантационный период с учетом молекулярно-генетических особенностей, в частности уровня экспрессии гена EVI1, может способствовать повышению эффективности противорецедивной терапии и улучшению результатов аллоТГСК.


Ключевые слова: хронический миелолейкоз (ХМЛ), аллогенная трансплантация гемопоэтических стволовых клеток (аллоТГСК), BCR-ABL, EVI1.

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