Механизм лимфомы Беркитта

На основании всех этих фактов можно предположить следующий механизм лимфомы Беркитта. В В- клетках вследствие транслокаций онкоген с-тус оказывается приближенным к усилителям транскрипции (во

обще усилители способны активировать транскрипцию на довольно значительном расстоянии от себя). Ген с- тус при этом экспрессируется столь же эффективно, как в нормальных В- клетках экспрессируются гены иммуноглобулинов. Синтез продукта гена с-тус становится частью специализированной функции клетки.

Есть указания на то, что такой механизм лежит в основе многих других злокачественных заболеваний, затрагивающих иммунную систему человека. Дж. Юнис из Медицинской школы Миннесотского университета разра

ботал новый метод окраски хромосом, который позволяет с высокой точностью обнаруживать изменения хромосом в раковых клетках. Его результаты, полученные с помощью этого метода, позволяют думать, что для большинства злокачественных изменений В-клеток характерны те или иные перестройки хромосом.

Транслокаиии между 14-й хромосомой и сегментами 11-й и 18-й хромосом часто встречаются при лимфомах В-клеток у взрослых, при хронических лейкемиях В-клеток и при множественной миеломе. В совокупности с нашими знаниями о роли локуса тяжелых цепей иммуноглобулинов, находящегося в 14-й хромосоме, в развитии лимфомы Беркитта это наблюдение лает основания считать, что в 11-й и 18-й хромосомах человека располагаются онкогены; такое предположение подтверждается опытами, проведенными в Вистаровском институте Е. Цудзимото в сотрудничестве с Юнисом и Ноуэллом. Мы установили, что точки разрывов неизменно располагаются в коротких сегментах 11-й и 18-й хромосом, кроме того, они всегда имеются перед участком 14-й

хромосомы, который кодирует константную область тяжелой цепи иммуноглобулина. Два гипотетических онкогена, локализующихся в 11-й и 18-й хромосомах, мы предложили обозначать bcl- и bcl-2 (сокращения английского словосочетания В-се11 lymphoma/leukemia, что означает лимфома/лейкемия В-клеток).

Наблюдения, сделанные при изучении лимфомы Беркитта, открывают два основных направления исследований. Первая задача — установить природу усилителей транскрип

ции. Каковы конкретные последовательности ДНК, образующие усилитель? Каким образом они усиливают транскрипцию строго определенных генов? Второе направление — изучение онкогена с-тус. В чем заключается функция гена с-тус в нормальной клетке и почему усиленная его экспрессия неизбежно вызывает злокачественную трансформацию?

 

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