Неопластические изменения В-клеток

Наша работа создает предпосылки для новых экспериментальных подходов к исследованию неопластических изменений В-клеток. Многие злокачественные заболевания связаны с транслокацией неизвестного онкогена в локус тяжелых цепей иммуноглобулинов в 14-й хромосоме. Локус тяжелых цепей изучен довольно подробно, и имеются ДНК-пробы, позволяющие исследовать прилегающие к нему участки ДНК. Поскольку в результате транслокацин онкоген, как правило, оказывается в непосредственной близости от локуса тяжелых цепей, эти ДНК-пробы могут служить инструментом для идентификации, выделения и характеристики генов, имеющих отношение к развитию большинства раковых заболеваний, поражающих В-клетки у человека. На этом пути исследований применение знаний о генетических механизмах, определяющих биосинтез антител, приведет к выяснению генетической структуры новых выделенных онкогенов.

На основе исследования хромосомных транслокаций могут быть также разработаны новые методы диагностики и изучения раковых заболеваний иммунной системы. Например, точки разрыва хромосом в злокачественных В-клетках с транслокациями между 11-й и 14-й или 14-й и 18-й хромосомами располагаются в пределах сравнительно коротких участков ДНК. Поэтому возможно создание ДНК-проб, специфичных по отношению к этим небольшим сегментам. С помощью таких проб в образце ткани, взятом из пораженной области организма, можно будет точно определить, какая хромосомная перестройка вызвала данное раковое заболевание.

Судя по самым последним данным, знания о злокачественных изменениях В-клеток применимы также к Т-клеткам — второму важнейшему компоненту иммунной системы. Кроче в сотрудничестве с Ровера, а также с М. Дэвисом из Станфордского университета обнаружили, что ген а- цепи рецептора Т-клеток локализован в том районе 14-й хромосомы, который участвует в некоторых трансло- кацнях, характерных для определенных видов рака Т-клеток.

Таким образом, значение установленного в наших работах механизма, лежащего в основе лимфомы Беркит- та, выходит за рамки этого конкретного заболевания. По-видимому, транслокации при лимфоме Беркитта могут служить моделью большинства злокачественных заболеваний В- клеток, а возможно, также и Т-клеток. Кроме того, выяснение механизма транслокации приведет к быстрому прогрессу в изучении не только других видов рака, но и механизмов контроля генетической экспрессии при нормальном развитии и функционировании иммунной системы человека.

 

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