Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New potential therapeutic target identified for Diffuse Large B-Cell Lymphoma

29.11.2011
Researchers reveal deletions and mutations of the FBXO11 gene in B-cells contribute to the development of the most common type of lymphoma

Researchers from the NYU Cancer Institute, an NCI-designated cancer center at NYU Langone Medical Center, have discovered a new potential therapeutic target for Diffuse Large B-Cell Lymphoma (DLBCL), the most aggressive and common type of lymphoma in adults. The new study, published in the November 23 issue of Nature, reveals the underlying molecular mechanism contributing to the development of lymphomagenesis.

"We have discovered that the protein FBXO11 is a novel tumor suppressor in B-cells," said senior study author Michele Pagano, MD, the May Ellen and Gerald Jay Ritter Professor of Oncology and Professor of Pathology at NYU Langone Medical Center and a Howard Hughes Medical Institute Investigator. "Our new research findings show deletion or mutation of the FBXO11 gene in B-cells may lead to the formation of Diffuse Large B-Cell Lymphoma."

Lymphoma is a blood cancer that affects the lymphatic system, the body's infection and disease-fighting network. DLBCL is the most common type of adult lymphoma. This type of non-Hodgkin lymphoma develops within B-cells, a type of lymphocytes or white blood cells in the lymphatic tissue of the body. Mutations of certain genes in the B-cells located in the lymph nodes and other organs of the immune system contribute to the proliferation of DLBCL throughout the body.

The majority of patients with DLBCL overexpress the protein B-Cell Lymphoma 6 (BCL6). By binding to specific DNA sequences, BCL6 regulates the transcription of genes that are crucial to B-cell development and function. Deregulation of BCL6 leads to the pathogenesis of B-cell lymphomas as proven in experiments in mice expressing BCL6 in B-cells and developing DLBCL similar to human disease. In certain DLBCL patients, BCL6 overexpression is achieved through gene translocation or mutation of its promoter. However, many other patients with DLBCLs overexpress BCL6 through a mechanism that has been unknown until now.

In the study, NYU Langone researchers show FBXO11 as a novel tumor suppressor. FBXO11, part of a SKP1/CUL1/F-box protein (SCF) ubiquitin ligase protein complex, controls BCL6 degradation. FBXO11 functions to keep the levels of BCL6 in B-cells low. The new study shows that BCL6 protein is targeted for degradation by the B-cell's ubiquitin system, the cell-recycling system that helps limit unnecessary cell growth and prevent malignant cell transformation. FBXO11-mediated elimination of BCL6 prevents the development of DLBCL. Additionally, researchers discovered FBXO11 is deleted or mutated in many DLBCL cell lines and DLBCL patients. Experimentally, inactivation, mutation or deletion of FBXO11 in B-cells induces overexpression of BCL6. Moreover, reconstitution of FBXO11 expression in FBXO11-deleted DLBCL cells, by promoting BCL6 degradation, inhibits proliferation and induces the death of tumor cells.

"These findings reveal the molecular mechanism behind the overexpression of BCL6 in B-cell lymphomas," said Dr. Pagano. "Mutations and deletions of FBXO11 in B-cells contribute to lymphomagenesis. As lymphoma cells are addicted to BCL6 expression, FBXO11-mediated regulation of BCL6 is a new potential therapeutic strategy for the future treatment of lymphoma."

This study was a collaboration between NYU Cancer Institute, NYU School of Medicine, Howard Hughes Medical Institute, University of Torino, San Giovanni Battista Hospital, Dana-Farber Cancer Institute. The study was supported by funding from the National Institutes of Health, Howard Hughes Medical Institute, Susan G. Komen Foundation and Lymphoma Research Foundation.

About NYU Langone Medical Center

NYU Langone Medical Center, a world-class, patient-centered, integrated, academic medical center, is one on the nation's premier centers for excellence in clinical care, biomedical research and medical education. Located in the heart of Manhattan, NYU Langone is composed of three hospitals – Tisch Hospital, its flagship acute care facility; the Rusk Institute of Rehabilitation Medicine, the world's first university-affiliated facility devoted entirely to rehabilitation medicine; and the Hospital for Joint Diseases, one of only five hospitals in the nation dedicated to orthopaedics and rheumatology – plus the NYU School of Medicine, which since 1841 has trained thousands of physicians and scientists who have helped to shape the course of medical history. The medical center's tri-fold mission to serve, teach and discover is achieved 365 days a year through the seamless integration of a culture devoted to excellence in patient care, education and research. For more information, go to http://www.NYULMC.org.

Lauren Woods | EurekAlert!
Further information:
http://www.nyumc.org

More articles from Life Sciences:

nachricht Overlooked molecular machine in cell nucleus may hold key to treating aggressive leukemia
23.04.2019 | Cincinnati Children's Hospital Medical Center

nachricht Bacteria use their enemy -- phage -- for 'self-recognition'
23.04.2019 | Chinese Academy of Sciences Headquarters

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Quantum gas turns supersolid

Researchers led by Francesca Ferlaino from the University of Innsbruck and the Austrian Academy of Sciences report in Physical Review X on the observation of supersolid behavior in dipolar quantum gases of erbium and dysprosium. In the dysprosium gas these properties are unprecedentedly long-lived. This sets the stage for future investigations into the nature of this exotic phase of matter.

Supersolidity is a paradoxical state where the matter is both crystallized and superfluid. Predicted 50 years ago, such a counter-intuitive phase, featuring...

Im Focus: Explosion on Jupiter-sized star 10 times more powerful than ever seen on our sun

A stellar flare 10 times more powerful than anything seen on our sun has burst from an ultracool star almost the same size as Jupiter

  • Coolest and smallest star to produce a superflare found
  • Star is a tenth of the radius of our Sun
  • Researchers led by University of Warwick could only see...

Im Focus: Quantum simulation more stable than expected

A localization phenomenon boosts the accuracy of solving quantum many-body problems with quantum computers which are otherwise challenging for conventional computers. This brings such digital quantum simulation within reach on quantum devices available today.

Quantum computers promise to solve certain computational problems exponentially faster than any classical machine. “A particularly promising application is the...

Im Focus: Largest, fastest array of microscopic 'traffic cops' for optical communications

The technology could revolutionize how information travels through data centers and artificial intelligence networks

Engineers at the University of California, Berkeley have built a new photonic switch that can control the direction of light passing through optical fibers...

Im Focus: A long-distance relationship in femtoseconds

Physicists observe how electron-hole pairs drift apart at ultrafast speed, but still remain strongly bound.

Modern electronics relies on ultrafast charge motion on ever shorter length scales. Physicists from Regensburg and Gothenburg have now succeeded in resolving a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

First dust conference in the Central Asian part of the earth’s dust belt

15.04.2019 | Event News

Fraunhofer FHR at the IEEE Radar Conference 2019 in Boston, USA

09.04.2019 | Event News

 
Latest News

Control 2019: Fraunhofer IPT presents high-speed microscope with intuitive gesture control

24.04.2019 | Trade Fair News

Marine Skin dives deeper for better monitoring

23.04.2019 | Information Technology

Geomagnetic jerks finally reproduced and explained

23.04.2019 | Earth Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>