ремиссия без лечения

KIR-генетические факторы и ответ на терапию ингибиторами тирозинкиназ при хроническом миелоидном лейкозе

ОБЗОРЫ , , ,

Е.В. Кузьмич1, И.Е. Павлова1, Л.Н. Бубнова1,2, С.С. Бессмельцев1

1 ФГБУ «Российский НИИ гематологии и трансфузиологии ФМБА России», ул. 2-я Советская, д. 16, Санкт-Петербург, Российская Федерация, 191024

2 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: Елена Витальевна Кузьмич, канд. биол. наук, ул. 2-я Советская, д. 16, Санкт-Петербург, Российская Федерация, 191024; тел.: +7(921)912-52-07; e-mail: yelenakuzmich@gmail.com

Для цитирования: Кузьмич Е.В., Павлова И.Е., Бубнова Л.Н., Бессмельцев С.С. KIR-генетические факторы и ответ на терапию ингибиторами тирозинкиназ при хроническом миелоидном лейкозе. Клиническая онкогематология. 2023;16(2):119–27.

DOI: 10.21320/2500-2139-2023-16-2-119-127

РЕФЕРАТ

Разработка и внедрение в клиническую практику ингибиторов тирозинкиназ (ИТК) значительно улучшили прогноз у пациентов с хроническим миелоидным лейкозом (ХМЛ). Примерно 50 % пациентов, достигающих глубокого молекулярного ответа, могут быть кандидатами на безопасное прекращение приема ИТК. Несмотря на достигнутые результаты, до настоящего времени не существует надежных биомаркеров для прогнозирования ответа и сохранения ремиссии без лечения после прекращения приема ИТК. Поскольку ИТК не уничтожают лейкозные стволовые клетки, остающиеся потенциальным источником рецидива, важную роль при ХМЛ играют естественные киллеры (NK-клетки), обладающие противоопухолевой активностью. Функциональная активность NK-клеток определяется уровнем экспрессии и репертуаром иммуноглобулиноподобных рецепторов киллерных клеток (KIR). Современные исследования свидетельствуют о том, что KIR-генотип пациента оказывает влияние на возможность достижения раннего и глубокого молекулярных ответов на ИТК первого и второго поколений, выживаемость без прогрессирования и общую выживаемость больных, а также сохранение ремиссии без лечения. На этом основании KIR-генетические факторы могут рассматриваться в качестве перспективных предикторов ответа на терапию ИТК у пациентов с ХМЛ. Ранние клинические исследования моноклональных антител, блокирующих ингибирующие KIR с целью повысить активность NK-клеток, показали приемлемые профиль безопасности и эффективность при некоторых гематологических заболеваниях (таких, как острый миелоидный лейкоз, множественная миелома, Т-клеточная лимфома) при использовании в комбинации с цитостатическими препаратами или противоопухолевыми моноклональными антителами. Определение KIR-генотипа при ХМЛ может способствовать разработке эффективных средств иммунотерапии этой злокачественной опухоли системы крови.

Ключевые слова: гены иммуноглобулиноподобных рецепторов киллерных клеток, ингибиторы тирозинкиназ, ремиссия без лечения, хронический миелоидный лейкоз.

Получено: 8 ноября 2022 г.

Принято в печать: 1 марта 2023 г.

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Биологические механизмы сохранения глубокого молекулярного ответа при хроническом миелолейкозе после отмены ингибиторов тирозинкиназ

ОБЗОРЫ , , ,

Е.Ю. Челышева, М.А. Гурьянова, А.Г. Туркина

ФГБУ «НМИЦ гематологии» Минздрава России, Новый Зыковский пр-д, д. 4, Москва, Российская Федерация, 125167

Для переписки: Екатерина Юрьевна Челышева, канд. мед. наук, Новый Зыковский пр-д, д. 4, Москва, Российская Федерация, 125167; e-mail: denve@bk.ru

Для цитирования: Челышева Е.Ю., Гурьянова М.А., Туркина А.Г. Биологические механизмы сохранения глубокого молекулярного ответа при хроническом миелолейкозе после отмены ингибиторов тирозинкиназ. Клиническая онкогематология. 2021;14(4):427–35.

DOI: 10.21320/2500-2139-2021-14-4-427-435

РЕФЕРАТ

Возможность наблюдения без лечения у пациентов с хроническим миелолейкозом (ХМЛ) в эру ингибиторов тирозинкиназ (ИТК) остается актуальным вопросом. В клинических исследованиях по отмене ИТК при стабильном глубоком молекулярном ответе показана вероятность сохранения молекулярной ремиссии у 40–60 % больных. Сохранение ремиссии без лечения (РБЛ) даже при персистировании остаточных лейкозных клеток свидетельствует о том, что существуют особые, биологически обусловленные механизмы контроля пролиферации опухолевых клеток, не зависящие от BCR-ABL-киназной активности. Поиск факторов, которые определяют различия кинетики остаточного лейкозного клона после отмены ИТК, — важная задача для понимания основ РБЛ как нового биологического явления. В обзоре представлены сведения мировой литературы, касающиеся изучения иммунных, генетических и других биологических механизмов, лежащих в основе контроля минимальной остаточной болезни после отмены ИТК у больных ХМЛ.

Ключевые слова: хронический миелолейкоз, ингибиторы тирозинкиназ, ремиссия без лечения, глубокий молекулярный ответ, минимальная остаточная болезнь.

Получено: 10 мая 2021 г.

Принято в печать: 23 августа 2021 г.

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