We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress
Sign In
Advertise with Us
INTEGRA BIOSCIENCES AG

Download Mobile App




Targeting EZH2 May Prevent Development of B-cell Lymphomas

By LabMedica International staff writers
Posted on 30 May 2013
Print article
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


Platinum Member
COVID-19 Rapid Test
OSOM COVID-19 Antigen Rapid Test
Specimen Collection & Transport
POCT Fluorescent Immunoassay Analyzer
FIA Go
Gold Member
ADAMTS-13 Protease Activity Test
ATS-13 Activity Assay

Print article

Channels

Clinical Chemistry

view channel
Image: Reaching speeds up to 6,000 RPM, this centrifuge forms the basis for a new type of inexpensive, POC biomedical test (Photo courtesy of Duke University)

POC Biomedical Test Spins Water Droplet Using Sound Waves for Cancer Detection

Exosomes, tiny cellular bioparticles carrying a specific set of proteins, lipids, and genetic materials, play a crucial role in cell communication and hold promise for non-invasive diagnostics.... Read more

Molecular Diagnostics

view channel
Image: MOF materials efficiently enrich cfDNA and cfRNA in blood through simple operational process (Photo courtesy of Science China Press)

Blood Circulating Nucleic Acid Enrichment Technique Enables Non-Invasive Liver Cancer Diagnosis

The ability to diagnose diseases early can significantly enhance the effectiveness of clinical treatments and improve survival rates. One promising approach for non-invasive early diagnosis is the use... Read more

Hematology

view channel
Image: The low-cost portable device rapidly identifies chemotherapy patients at risk of sepsis (Photo courtesy of 52North Health)

POC Finger-Prick Blood Test Determines Risk of Neutropenic Sepsis in Patients Undergoing Chemotherapy

Neutropenia, a decrease in neutrophils (a type of white blood cell crucial for fighting infections), is a frequent side effect of certain cancer treatments. This condition elevates the risk of infections,... Read more

Pathology

view channel
Image: The OvaCis Rapid Test discriminates benign from malignant epithelial ovarian cysts (Photo courtesy of INEX)

Intra-Operative POC Device Distinguishes Between Benign and Malignant Ovarian Cysts within 15 Minutes

Ovarian cysts represent a significant health issue for women globally, with up to 10% experiencing this condition at some point in their lives. These cysts form when fluid collects within a thin membrane... Read more
Copyright © 2000-2024 Globetech Media. All rights reserved.