New potential therapeutic target identified for Diffuse Large B-Cell 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."
Provided by New York University School of Medicine
- Small molecule targets B cell lymphoma Apr 12, 2010 | not rated yet | 0
- Novel test identifies leukemia patients likely to respond to new therapy Feb 20, 2007 | not rated yet | 0
- New lymphoma therapy may be more effective with fewer side effects Nov 03, 2010 | not rated yet | 0
- Scientists design new drug type to kill lymphoma cells May 11, 2010 | not rated yet | 0
- Ensuring the persistence of immune memory Sep 16, 2011 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
How can there be a term called "intestinal metaplasia" of stomach
9 hours ago Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
Ratio of Hydrogen of Oxygen in Dessicated Animal Protein
May 13, 2013 As an experiment, for the past few months I've been consuming at least one portion of Jell-O or unflavored Knox gelatin per day. I'm 64, in very...
Alcohol and acetaminophen
May 13, 2013 Edit: sorry for the typo in the title , can't edit I looked around on google quite a bit and it's very hard to find precise information on the...
- More from Physics Forums - Medical Sciences
More news stories
A study of veterans at high risk for developing lung cancer shows that low-dose computed tomography (LDCT) can be highly effective in helping clinicians spot tiny lung nodules which, in a small number of patients, may indicate ...
Cancer 1 hour ago | not rated yet | 0
An attack on glioblastoma brain tumor cells that uses a modified poliovirus is showing encouraging results in an early study to establish the proper dose level, researchers at Duke Cancer Institute report.
Cancer 2 hours ago | not rated yet | 0
The surgical management of non-small cell lung cancer (NSCLC) in U.S. hospitals varies widely depending on the race of the patient, according to a new study.
Cancer 6 hours ago | not rated yet | 0
Treatment with an Alpha-1 proteinase inhibitor (A1-PI), a naturally occurring protein that protects lung tissue from breakdown and protects the lung's elasticity, is effective in slowing the progression of emphysema in patients ...
Cancer 7 hours ago | not rated yet | 0
Scientists from Nanyang Technological University (NTU) and Lund University, Sweden, have bioengineered a novel molecule which has been proven to successfully kill tumour cells.
Cancer 7 hours ago | 5 / 5 (1) | 0
A drug commonly used to treat depression and anxiety may improve a stress-related heart condition in people with stable coronary heart disease, according to researchers at Duke Medicine.
30 minutes ago | not rated yet | 0 |
(HealthDay)—The overall health of Americans isn't improving much, with about six in 10 people either overweight or obese and large numbers engaging in unhealthy behaviors like smoking, heavy drinking or ...
40 minutes ago | not rated yet | 0
(HealthDay)—In 2008 to 2010, the prevalence of key health behaviors among U.S. adults varied, with about one in five adults current smokers and 62.1 percent overweight or obese, according to a report presented ...
30 minutes ago | not rated yet | 0
(HealthDay)—Factors such as increased case finding may explain why Michigan had half of the total spinal infections associated with contaminated methylprednisolone acetate in the recent fungal meningitis ...
20 minutes ago | not rated yet | 0
Early use of tracheostomy for mechanically ventilated patients not associated with improved survival
For critically ill patients receiving mechanical ventilation, early tracheostomy (within the first 4 days after admission) was not associated with an improvement in the risk of death within 30 days compared to patients who ...
30 minutes ago | not rated yet | 0
(HealthDay)—Three-quarters of public schools in the metro Atlanta area contain microbes, including bacteria indicating the presence of fecal matter, according to research published in the May 17 issue of ...
10 minutes ago | not rated yet | 0