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A new target for lymphoma therapy
Date:12/9/2009

Researchers at the Program in Cellular and Molecular Medicine and the Immune Disease Institute at Children's Hospital Boston (PCMM/IDI) have found a link between a common mutation that can lead to cancer and a distant gene regulator that enhances its activity. Discovery of this relationship could lead to drugs targeting B-cell lymphomas, including Burkitt's lymphoma, an aggressive cancer in children, as well as multiple myelomas and other blood-related cancers.

Lymphomas often originate in B cells, the same cells that produce antibodies to help fight infections. A B cell can become cancerous if a gene known as c-myc leaps to another section of DNA (the IgH region, responsible for building antibodies), fuses with it, and somehow becomes over-activated. Scientists have wondered for years how this oncogenic activation occurs, in particular what component in the IgH region activates c-myc. The new study, published in the Dec. 10 issue of Nature, identifies this regulatory component, and marks the first time researchers are able to understand how this movement of genes, or "chromosomal translocation," can hijack a B cell's operation badly enough to lead to cancer.

"IgH-to-myc translocation is the classic example of activation of an oncogene in cancer," says Frederick Alt, PhD, scientific director of PCMM/IDI and senior author of the study. "But nobody really understood how it works."

Aberrant DNA translocations can occur during two different stages of a B cell's development: during a process known as VDJ recombination, when a progenitor B cell creates an antibody to fight a specific pathogen, or during class switch recombination, when a mature B cell gives its antibody a different strategy to fight infection (changing from an IgM to an IgG antibody, for example). Based on their past research , Alt and his colleagues decided to focus on one part of the IgH region called IgH 3' regulatory region (IgH3'RR). They had already shown Ig
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Contact: Rob Graham
Rob.Graham@childrens.harvard.edu
617-919-3110
Children's Hospital Boston
Source:Eurekalert  

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