Expression und Funktion von LEF-1, einem Signaturgen des molekularen Burkitt Lymphoms, in malignen Lymphomen

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Burkitt Lymphoma (BL) is a highly malignant, aggressive Non-Hodgkin Lymphoma. We have developed a molecular definition of BL and identified LEF1 as a signature gene for BL. We have shown aberrant LEF1 expression in BLs thus approving our starting hypothesis of SP3. LEF1 knockdown in BL lines was associated with cell cycle arrest and reduced proliferation. New LEF1 target genes were identified by microarray analysis. We will now address the following questions: (1) What is the mode of action of LEF1 in BL and (ii) what is the mechanism leading to aberrant LEF1 expression? To answer the first question we will continue the characterization of LEF1 target genes including the characterization of LEF1 binding sites (ChlP-Seq) and how LEF1 regulates its target genes to sustain the malignant properties of BLs (by overexpression/knockdown of target genes). Furthermore, we will perform a systematic search for proteins interacting with LEF1 in lymphoma cells. To answer the second question we will analyse the regulation of LEF1 expression in BL and BL precursor cells identifying pathways involved in activating or inhibiting the LEF1 promoter. In order to characterise LEF1 mediated oncogenic modules as potenfial prognostic or therapeutic marker in vitro data will be evaluated on large scale lymphoma gene expression profiles.