нарушения сигнальных путей

Молекулярно-генетические нарушения в патогенезе опухолей системы крови и соответствующие им изменения сигнальных систем клетки

ОБЗОРЫ , , ,

Л.Р. Тилова1, А.В. Савинкова1, Е.М. Жидкова1,2, О.И. Борисова1,3, Т.И. Фетисов1,4, К.А. Кузин1, О.А. Власова1, А.С. Антипова3, О.Ю. Баранова3, К.И. Кирсанов1, Г.А. Белицкий1, М.Г. Якубовская1, Е.А. Лесовая1,5

1 НИИ канцерогенеза, ФГБУ «Российский онкологический научный центр им. Н.Н. Блохина» Минздрава России, Каширское ш., д. 24, Moсква, Российская Федерация, 115478

2 Московский технологический университет, пр-т Вернадского, д. 78, Москва, Российская Федерация, 119454

3 НИИ клинической онкологии, ФГБУ «Российский онкологический научный центр им. Н.Н. Блохина» Минздрава России, Каширское ш., д. 23, Moсква, Российская Федерация, 115478

4 Первый Московский государственный медицинский университет им. И.М. Сеченова, ул. Трубецкая, д. 8, корп. 2, Москва, Российская Федерация, 119991

5 Рязанский государственный медицинский университет им. И.П. Павлова, ул. Высоковольтная, д. 9, Рязань, Российская Федерация, 390026

Для переписки: Екатерина Андреевна Лесовая, канд. биол. наук, Каширское ш., д. 24, стр. 15, Moсква, Российская Федерация, 115478; тел.: 8(910)471-41-28; e-mail: lesovenok@yandex.ru

Для цитирования: Тилова Л.Р., Савинкова А.В., Жидкова Е.М. и др. Молекулярно-генетические нарушения в патогенезе опухолей системы крови и соответствующие им изменения сигнальных систем клетки. Клиническая онкогематология. 2017;10(2):235–49.

DOI: 10.21320/2500-2139-2017-10-2-235-249

РЕФЕРАТ

Заболевания системы крови включают широкую группу злокачественных опухолей кроветворной и лимфоидной тканей, в основе патогенеза которых лежат генетические изменения, специфические для каждой отдельной разновидности нозологий. Одной из характерных особенностей онкогематологических заболеваний является высокая частота хромосомных аномалий (делеции, транслокации, инсерции). Кроме того, наблюдаются также мутации отдельных генов или блокирование нормальной регуляции функционирования генов в связи с эпигеномными событиями. Прогрессирование онкогематологических заболеваний может быть обусловлено накоплением различных генетических нарушений. Современная классификация опухолей кроветворной и лимфоидной тканей основана на анализе клинических данных, морфологических и функциональных признаков опухолевых клеток и выявлении специфических цитогенетических и молекулярно-генетических нарушений. К настоящему времени установлено большое количество генетических нарушений, характерных для конкретных типов злокачественных новообразований системы крови. Это позволяет оптимизировать лечебную тактику, а также разрабатывать, тестировать и вводить в клиническое использование ряд таргетных препаратов. К ним относятся препараты на основе моноклональных антител (ритуксимаб, алемтузумаб и др.), низкомолекулярные соединения (иматиниб, бортезомиб, карфилзомиб). Для разработки новых таргетных молекул или же перепрофилирования уже известных химиопрепаратов не только полезна информация об аномалиях при каждом типе гематологической опухоли, но и понимание изменений в эфферентных путях передачи сигнала в клетке, которые затрагивают данное нарушение. В настоящем обзоре рассматриваются генетические нарушения при заболеваниях, обозначенных в международной классификации ВОЗ опухолей кроветворной и лимфоидной тканей 2008 г. и дополненной в 2016 г., и соответствующие изменения в сигнальных путях, связанные со злокачественной трансформацией клеток кроветворной системы.

Ключевые слова: опухоли кроветворной и лимфоидной тканей, хромосомные аномалии, нарушения сигнальных путей, классификация ВОЗ.

Получено: 29 сентября 2016 г.

Принято в печать: 16 января 2017 г.

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