Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists Find Key Pathway Implicated in Progression of Childhood Cancer

14.09.2010
New Finding May Pave the Way to the Development of Drugs for Treating the Disease

According to a new study a protein crucial for the immune response appears to be a key player in the progression of a devastating form of childhood leukemia called T-cell acute lymphoblastic leukemia (T-ALL). Suppressing the activity of the protein kills the leukemic cells, the study shows, opening a potential avenue to new drugs that could prevent progression of the disease.

Led by Iannis Aifantis, PhD, associate professor of pathology and director of the Cancer Stem Cell Program at the NYU Cancer Institute at NYU Langone Medical Center, and colleagues at the Institute Municipal d’Investigacions Mediques in Barcelona, Spain, the new study appears in the September 14, 2010, issue of Cancer Cell. These molecular detectives discovered the protein by picking up on a bit of cross-talk, or conversation, between two unrelated genes.

“We are very excited about this discovery because small molecule drugs that block this protein are already in development,” said Aifantis, who is also a Howard Hughes Medical Institute Early Career Scientist. “We plan to continue to study these inhibitors in the laboratory with the aim of evaluating the feasibility of testing such drugs in patients.

Despite great strides in treating childhood leukemia, T-ALL, poses special challenges because of the high risk of leukemic cells invading the brain and spinal cord of children who relapse. T-ALL, a blood-borne cancer in which the bone marrow makes too many lymphocytes, or white blood cells, strikes several hundred children and adolescents in the U.S. annually. While more than 90 percent initially go into remission through a combination of chemotherapy and radiation, up to one third of this group eventually relapse.

Previous research had strongly implicated a well-known oncogene, or cancer-causing gene, called Notch1 in the initiation and progression of T-ALL in patients. Certain kinds of mutations in this gene have been found in nearly half of T-ALL patients and current estimates suggest that the gene’s regulatory influence might be implicated in nearly 90 percent of cases.

In the new study, the researchers found that Notch targeted a protein called NF-kB (short for nuclear factor kB), an important transcription factor that regulates genes involved in cell division and the immune response. Transcription factors bind to the DNA of genes, thereby activating them. Previous studies had suggested that cross talk between Notch and NF-kB occurred, but the new study reveals the molecular characters involved in the cross talk, and shows that blocking NF-kB eliminated leukemic cells carrying activating Notch mutations.

The researchers then found that the way that Notch1 can induce NF-kB signaling is by suppressing the expression of an enzyme called CYLD, a negative regulator of the NF-kB pathway. In other words, the enzyme normally shuts down the pathway of genes regulated by NF-kB.

“Presently, drugs that inhibit NF-kB are already in development and some of them are being tested in humans for inflammatory diseases,” said Dr. Aifantis, “If used for patients with T-ALL leukemia, such drugs could be used alone or in combination with more established protocols like chemotherapy and radiation.”

Co-authors of the study include Luis Espinosa and Anna Bigas of the Institute Municipal d’Investigacions Mediques in Barcelona Spain, as well as Severine Cathelin, Thomas Trimarchi and Alexander Statnikov of NYU Langone Medical Center.

The study was supported by grants from the National Institutes of Health in Bethesda, Maryland, The Howard Hughes Medical Institute in Chevy Chase, Maryland and the American Cancer Society.

About NYU Langone Medical Center
NYU Langone Medical Center is one of the nation's premier centers of excellence in healthcare, biomedical research, and medical education. For over 170 years, NYU physicians and researchers have made countless contributions to the practice and science of health care. Today the Medical Center consists of NYU School of Medicine, including the Smilow Research Center, the Skirball Institute of Biomolecular Medicine, and the Sackler Institute of Graduate Biomedical Sciences; and the NYU Hospitals Center, including Tisch Hospital, a 705-bed acute-care general hospital, Rusk Institute of Rehabilitation Medicine, the first and largest facility of its kind, and NYU Hospital for Joint Diseases, a leader in musculoskeletal care, a Clinical Cancer Center and numerous ambulatory sites.

Dorie Klissas | Newswise Science News
Further information:
http://www.nyumc.org

More articles from Life Sciences:

nachricht Warming ponds could accelerate climate change
21.02.2017 | University of Exeter

nachricht An alternative to opioids? Compound from marine snail is potent pain reliever
21.02.2017 | University of Utah

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Impacts of mass coral die-off on Indian Ocean reefs revealed

21.02.2017 | Earth Sciences

Novel breast tomosynthesis technique reduces screening recall rate

21.02.2017 | Medical Engineering

Use your Voice – and Smart Homes will “LISTEN”

21.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>