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New key element discovered in pathogenesis of Burkitt lymphoma
Date:8/13/2012

Burkitt lymphoma is a malignant, fast-growing tumor that originates from a subtype of white blood cells called B lymphocytes of the immune system and often affects internal organs and the central nervous system. Now Dr. Sandrine Sander and Professor Klaus Rajewsky of the Max Delbrck Center for Molecular Medicine (MDC) Berlin-Buch have identified a key element that transforms the immune cells into malignant lymphoma cells. They developed a mouse model that closely resembles Burkitt lymphoma in humans and that may help to test new treatment strategies (Cancer Cell)*.

Burkitt lymphoma typically develops in childhood and occurs most frequently in equatorial Africa and South America. This tumor originates from germinal centers of the lymphoid organs (Peyer's patches in the small intestine, lymph nodes and spleen). The germinal center reaction is initiated by mature B cells upon detection of a foreign substance (antigen). These B cells modify their DNA in the course of the reaction, resulting finally in a highly specific antibody response against the antigen.

The B cell receptor (BCR), an antibody presented on the surface of mature B cells, plays a crucial role in the germinal center reaction. In order to optimally recognize the respective antigen and initiate an appropriate immune response, the DNA segments encoding the antibody need to be modified and rearranged. While the processes are complex, DNA breaks occur and error-prone repair mechanisms may lead to genetic mutations associated with cancer development.

It is well established that in Burkitt lymphoma, mistakes in the repair of DNA breaks result in the translocation of the c-MYC oncogene. This gene regulates cell division, and thus its expression is tightly controlled in normal cells. The c-MYC translocation leads to its deregulation, and the affected cells divide in an uncontrolled manner. However, c-MYC overexpression also leads to massive cell death. Therefore c-MYC dereg
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Contact: bachtler@mdc-berlin.de
bachtler@mdc-berlin.de
49-309-406-3896
Helmholtz Association of German Research Centres
Source:Eurekalert

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