Роль факторов гипоксии в транскрипционных механизмах клонального гемопоэза при миелодиспластическом синдроме

Гипоксия-индуцируемый фактор (Hypoxia-induced factor, HIF), главный регулятор клеточного ответа на гипоксию, координирует адаптацию через активацию генов, контролирующих ангиогенез (Vascular Endothelial Growth Factor, VEGF), метаболизм глюкозы (Glucose Transporter, GLUT1, GLUT3), пролиферацию (Insulin-like Growth Factor, IGF-2), pH-гомеостаз (Carbonic anhydrase, CA IX) и эритропоэз (ЭПО). Роль HIF как маркера гипоксии и драйвера агрессивности солидных опухолей не вызывает сомнений, однако его вклад в патогенез гематологических заболеваний, в частности в развитие клонального кроветворения и лейкемогенез, остается малоизученным и противоречивым. В данном обзоре литературы мы сосредоточились на анализе взаимосвязи экспрессии HIF-1α (наиболее изученной изоформы) с риском возникновения клонального гемопоэза при миелодиспластическом синдроме (МДС), возможностью последующей трансформации в острый миелобластный лейкоз (ОМЛ) и неблагоприятным прогнозом течения МДС в целом. Особое внимание уделено потенциальным механизмам, посредством которых гипоксия и HIF-1α могут способствовать селективному преимуществу диспластического клона (например, через изменение метаболизма, апоптоза или взаимодействия со стромой костного мозга) и его злокачественной прогрессии. Полученные данные важны для оценки риска течения МДС и поиска новых терапевтических мишеней коррекции возникших нарушений.

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