Navigation Links
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 deregulation by itself is unable to transform normal cells into cancer cells. In Burkitt lymphoma, the apoptosis induction of elevated c-MYC expression must be overcome by additional mutations preventing cell death.

Recently, Professor Rajewsky and his colleagues showed that an enzyme called PI3K is critical for the survival of mature B cells. It activates a signaling pathway that regulates cell growth and counteracts programmed cell death. Based on these findings Dr. Sander and Professor Rajewsky investigated an interaction of c-MYC and PI3K in mouse tumorigenesis in their present study. They demonstrated that PI3K is a key element in Burkitt lymphoma development which enables c-MYC to turn germinal center B lymphocytes into lymphoma cells that divide continuously and escape apoptosis.

However, not every B cell co-expressing c-MYC and PI3K transforms into a lymphoma cell, thus the researchers suspected additional genetic mutations that may play a role in Burkitt lymphomagenesis. Indeed they could identify such aberrations in their mouse model, and a study in human Burkitt lymphoma by Professor Louis Staudt (National Cancer Institute, Bethesda, Maryland, USA), which was published simultaneously in Nature (DOI: 10.1038/nature11378), confirmed these results. Staudt and colleagues showed that Burkitt lymphoma patients, besides having mutations resulting in the activation of the PI3K signaling pathway, carry genetic mutations that resemble those in the mouse.

"In addition to c-MYC deregulation, the activation of the PI3K signaling pathway is a key element in the development of Burkitt lymphoma," said Dr. Sander and Professor Rajewsky. "The inhibition of this signaling pathway could therefore be an effective strategy for treating the disease."


'/>"/>

Contact: bachtler@mdc-berlin.de
bachtler@mdc-berlin.de
49-309-406-3896
Helmholtz Association of German Research Centres
Source:Eurekalert

Related biology news :

1. First direct evidence that elemental fluorine occurs in nature
2. Unexpected crustacean diversity discovered in northern freshwater ecosystems
3. University of Alberta led research may have discovered how memories are encoded in our brains
4. Newly discovered foot points to a new kid on the hominin block
5. New immune defense enzyme discovered
6. New genetic mechanism of immune deficiency discovered
7. Housekeeping mechanism for brain stem cells discovered
8. Scientists have discovered genes that increase the risk of osteoporosis and fractures
9. New form of intellectual disability discovered
10. 24 new species of lizards discovered on Caribbean islands are close to extinction
11. Key proteins newly discovered form and function may provide novel cancer treatment target
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:10/4/2017)... Oct. 4, 2017  GCE Solutions, a global clinical research organization ... document anonymization solution on October 4, 2017. Shadow is designed to ... comply with policy 0070 of the European Medicines Agency (EMA) in ... ... ...
(Date:7/20/2017)... , July 20, 2017 Delta (NYSE: DAL ) ... any Delta aircraft at Reagan Washington National Airport (DCA). ... Delta launches biometrics to board ... Delta,s biometric boarding ... Club is now integrated into the boarding process to allow eligible ...
(Date:6/14/2017)... IBM ) is introducing several innovative partner startups at ... between startups and global businesses, taking place in ... startups will showcase the solutions they have built with IBM ... France is one of the most ... increase in the number of startups created between 2012 and ...
Breaking Biology News(10 mins):
(Date:10/12/2017)... ... October 12, 2017 , ... ... announced today that they have entered into a multiyear collaboration to identify and ... researchers with additional tools for gene editing across all applications. , Under the ...
(Date:10/12/2017)... ... October 12, 2017 , ... ... launched Rosalind™, the first-ever genomics analysis platform specifically designed for life science ... in honor of pioneering researcher Rosalind Franklin, who made a major contribution ...
(Date:10/11/2017)... ... 11, 2017 , ... ComplianceOnline’s Medical Device Summit is back for its 4th ... in San Francisco, CA. The Summit brings together current and former FDA office bearers, ... and government officials from around the world to address key issues in device compliance, ...
(Date:10/11/2017)... ... 2017 , ... Disappearing forests and increased emissions are the main causes of ... year. Especially those living in larger cities are affected by air pollution related diseases. ... most pollution-affected countries globally - decided to take action. , “I knew I had ...
Breaking Biology Technology: