New key element discovered in pathogenesis of Burkitt lymphoma

August 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 Delbrück 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 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 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 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 ," said Dr. Sander and Professor Rajewsky. "The inhibition of this signaling pathway could therefore be an effective strategy for treating the disease."

Explore further: Lymphoma therapy could deliver a double punch

More information: Synergy between PI3K signalling and MYC in Burkitt lymphomagenesis, Cancer Cell, 2012.

Related Stories

Lymphoma therapy could deliver a double punch

April 30, 2012
B cell lymphomas are a group of cancers of that originate in lymphoid tissue from B cells, the specialized immune cell type that produces antibodies. The development of B cell lymphoma is associated with several known genetic ...

'If Hamlet give the first or second hit': The development of Burkitt's lymphoma

November 8, 2011
The human c-myc gene encodes a transcription factor (MYC) involved in the regulation of a vast number of other genes – it has been estimated that the transcription of about one in six genes is somehow under the control ...

Scientists identify a critical tumor suppressor for cancer

August 2, 2012
Scientists from the Florida campus of The Scripps Research Institute have identified a protein that impairs the development and maintenance of lymphoma (cancer of the lymph nodes), but is repressed during the initial stages ...

Protein may represent a switch to turn off B cell lymphoma

May 7, 2012
Researchers studying the molecular signals that drive a specific type of lymphoma have discovered a key biological pathway leading to this type of cancer. Cancerous cells have been described as being "addicted" to certain ...

Recommended for you

How a non-coding RNA encourages cancer growth and metastasis

August 21, 2017
A mechanism that pushes a certain gene to produce a non-coding form of RNA instead of its protein-coding alternative can promote the growth of cancer, report researchers at the Medical University of South Carolina (MUSC) ...

Spaser can detect, kill circulating tumor cells to prevent cancer metastases, study finds

August 21, 2017
A nanolaser known as the spaser can serve as a super-bright, water-soluble, biocompatible probe capable of finding metastasized cancer cells in the blood stream and then killing these cells, according to a new research study.

Comprehensive genomic analysis offers insights into causes of Wilms tumor development

August 21, 2017
A comprehensive genomic analysis of Wilms tumor - the most common kidney cancer in children - found genetic mutations involving a large number of genes that fall into two major categories. These categories involve cellular ...

Comparison of screening recommendations indicates annual mammography

August 21, 2017
When to initiate screening for breast cancer, how often to screen, and how long to screen are questions that continue to spark emotional debates. A new study compares the number of deaths that might be prevented as a result ...

Vitamin C may encourage blood cancer stem cells to die

August 17, 2017
Vitamin C may "tell" faulty stem cells in the bone marrow to mature and die normally, instead of multiplying to cause blood cancers. This is the finding of a study led by researchers from Perlmutter Cancer Center at NYU Langone ...

Outdoor light at night linked with increased breast cancer risk in women

August 17, 2017
Women who live in areas with higher levels of outdoor light at night may be at higher risk for breast cancer than those living in areas with lower levels, according to a large long-term study from Harvard T.H. Chan School ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.