Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING
JIB
BioConferenceLive

Targeting EZH2 May Prevent Development of B-cell Lymphomas

By BiotechDaily International staff writers
Posted on 30 May 2013
Image: Senior author Dr. Ari Melnick (Photo courtesy of Weill Cornell Medical College).
Image: Senior author Dr. Ari Melnick (Photo courtesy of Weill Cornell Medical College).
A "master regulator" gene has been identified in immune system B-cell lymphocytes that when mutated fails to maintain the normal cell phenotype, which prompts the B-cells to enter a phase of uncontrolled cell division that results in the type of cancer known as B-cell lymphoma.

Most B-cell lymphomas arise from germinal center (GC) B-cells, since they divide rapidly while at the same time mutating their antibody genes. In some cases other genes become mutated as well, which can eventually result in lymphoma formation. GCs are sites within lymph nodes where mature B lymphocytes rapidly proliferate, differentiate, mutate their antibodies, and class switch their antibodies during a normal immune response to an infection. GCs are an important part of the B-cell humoral immune response, and they develop dynamically after the activation of B-cells by T-dependent antigen.

Investigators at Weill Cornell Medical College (New York, NY, USA) examined the role of the protein encoded by the EZH2 (enhancer of zeste homolog 2, also known as histone-lysine N-methyltransferase) gene, which is highly expressed in GC B-cells, in the process leading up to lymphoma formation.

They reported in the May 13, 2013, issue of the journal Cancer Cell that EZH2 repressed proliferation checkpoint genes and helped establish chromatin domains at key regulatory loci to transiently block the differentiation of B-cells away from the GC phenotype. Genomic deletion or pharmacologic suppression of EZH2 expression with a chemical inhibitor suppressed GC formation and function.

"EZH2 is a master regulator protein that turns off the brakes that prevent cell division, so it allows cells to divide without stopping," said senior author Dr. Ari Melnick, professor of medicine at Weill Cornell Medical College. "EZH2 prevents germinal cells from transitioning to antibody-secreting cells. Indeed, in the normal immune system EZH2 prevents B-cells from exiting germinal centers so that these cells can continue to undergo sustained rapid cell division, which continues until the immune system says to stop. Then EZH2 goes away, and B-cells can develop into antibody-secreting cells, which send antibodies into the circulation to fight off infection. Germinal center cells absolutely require EZH2 and the lymphomas that arise from germinal center cells inherit that need regardless of whether they have mutations."

"Researchers had thought EZH2 inhibitors would only help patients with a mutation in their EZH2 gene, which represents a small subset of lymphoma patients. What we found is that a majority of lymphomas turn out to be dependent on normal EZH2, not just mutated EZH2," said Dr. Melnick. "Our research indicates that these inhibitors will be remarkably effective. I am very optimistic."

Related Links:

Weill Cornell Medical College



comments powered by Disqus

Channels

Drug Discovery

view channel
Image: Molecular rendering of the crystal structure of parkin (Photo courtesy of Wikimedia Commons).

Cinnamon Feeding Blocks Development of Parkinson's Disease in Mouse Model

A team of neurological researchers has identified a molecular mechanism by which cinnamon acts to protect neurons from damage caused by Parkinson's disease (PD) in a mouse model of the syndrome.... Read more

Therapeutics

view channel
Image: This type of electronic pacemaker could become obsolete if induction of biological pacemaker cells by gene therapy proves successful (Photo courtesy of Wikimedia Commons).

Gene Therapy Induces Functional Pacemaker Cells in Pig Heart Failure Model

Cardiovascular disease researchers working with a porcine heart failure model have demonstrated the practicality of using gene therapy to replace implanted electronic pacemakers to regulate heartbeat.... Read more

Lab Technologies

view channel

Precise Ion Irradiation Dosing Method Developed for Cancer Therapy

Scientists are employing nuclear physics principles to provide more effective approaches to radiotherapy treatment for cancer patients. Radiation therapy using heavy ions is best suitable for cancer patients with tumors that are difficult to access, such as in the brain. These particles scarcely damage the penetrated... Read more

Business

view channel

Cancer Immunotherapy Sector Predicted to Surge to USD 9 Billion Across Major Pharma Through 2022

The immunotherapy market will experience substantial growth through 2022, increasing from USD 1.1 billion in 2012 to nearly USD 9 billion in 2022 (corresponding to 23.8% annual growth) in the United Kingdom, United States, France, Germany, Italy, Spain, and Japan, according to recent market research. This notable growth... Read more
 
Copyright © 2000-2014 Globetech Media. All rights reserved.