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!
Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory
Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP
Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.
Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
09.12.2016 | Life Sciences
09.12.2016 | Ecology, The Environment and Conservation
09.12.2016 | Health and Medicine