Молекулярный анализ ГФИ-дефицитного клонального гематопоэза в пароксизмальной ночной гемоглобинурии

Пароксизмальная ночная гемоглобинурия (ПНГ) — приобретенный ютональный дефект гематопоэтических стволовых клеток, характеризующийся появлением клеток периферической крови, имеющих дефицит гликозилфосфатидилинозитол (ГФИ) — заякоренных поверхностных белков. Такими белками являются ингибиторы активации комплемента CD55 и CD59, недостаток которых и вызывает гиперчувствительность эритроцитов ПНГ пациентов к комплементу, приводящую к интраваскулярному гемолизу. Причиной ГФИ-дефицита являются мутации в гене PIG-A, продукт которого является одним из ключевых ферментов в биосинтезе ГФИ-якоря.

Однако механизм, позволяющий ГФИ-дефицитным гематопоэтическим стволовым клеткам при ПНГ доминировать в костном мозге и вносить значительный вклад в гематопоэз, до сих пор остается необъясненным. Показано, что мутации гена PIG-A не являются достаточным условием для клональной экспансии и развития ПНГ. В ПНГ, также как в, А А и МДС, были обнаружены генетическая нестабильность и увеличенная частота мутации. Поэтому представляется вероятным наличие дополнительных генетических изменений, мутаций или дифференциальной экспрессии генов, приводящих к клональной экспансии ГФИ-дефицитных гематопоэтических стволовых клеток костного мозга в ПНГ.

Б связи с вышеизложеным цель настоящего исследования состояла в изучении молекулярных основ клональной экспансии в ПНГ и идентификации генов, дифференциально экспрессированных в нормальных и ГФИ-дефицитных клетках ПНГ пациентов, анализе найденных генов, подтверждении их дифференциальной экспрессии и их характеристика в ПНГ.

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