Bedeutung von Transkriptionsfaktoren für die Pathogenese kutaner Lymphome^[*]

Zusammenfassung

Transkriptionsfaktoren sind DNA-bindende Proteine, die bei Eukaryoten an der Kontrolle der Transkription beteiligt sind, indem sie mit hoher Spezifität an jeweils passende Bereiche eines Promotors oder Enhancers binden. Sie können selbst einzelne Gene, aber auch komplexe Netzwerke allein regulieren. Dementsprechend kann eine Alteration eines solitären Transkriptionsfaktors zu minimalen, aber auch massiven Veränderungen bis hin zur Krebsentstehung führen. In der normalen Lymphozytenentwicklung reguliert ein Netzwerk von Transkriptionsfaktoren wie E2a, ID-2, NOTCH und PAX5 die Linienzugehörigkeit eines Lymphozyten und seinen Weg, sich zu einer B-, T-, NK- oder plasmozytoiden dendritischen Zelle zu entwickeln. Alterationen dieser Gene durch Mutationen oder auch Aktivierung von Inhibitoren einzelner Transkriptionsfaktoren können zu einer gestörten Lymphozytenentwicklung bis hin zur malignen Entartung führen.

Für das Sézary-Syndrom konnten wir erstmals zeigen, dass eine genomische Deletion des Transkriptionsfaktors E2A in der Mehrzahl der Fälle (70 %) nachzuweisen ist und pathogenetisch über eine Deregulation einer Reihe von Onkogenen und weiteren Transkriptionsfaktoren für Proliferation und Transformation ursächlich ist.

Abstract

Transcription factors are DNA-binding proteins involved in transcription processes in eukaryotes, by binding parts of promoters or enhancers with high specificity. They can thus regulate genes or complex networks by themselves. On this basis, alteration of a solitary transcription factor may lead to various cellular changes and also to neoplasia. A network of transcription factors, such as E2a, ID-2, NOTCH and PAX5 regulates lymphocytic development into B-, T-, NK- or plasmocytoid dendritic cells. Alterations of these genes via mutation or activation of inhibitors my lead to developmental disorders and also to malignant transformation.

In our own investigations we have shown that in Sezary's syndrome genomic deletion of transcription factor E2A may be detected in 70 % of the cases, resulting in deregulation of a series of oncogenes and other transcription factors responsible for cell proliferation and transformation.

^* Nach einem Vortrag anlässlich des 11. Jahressymposiums der Berliner Stiftung für Dermatologie am 2. Juli 2011, Berlin.

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