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 Stiffness matters
22.02.2018 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht Separate brain systems cooperate during learning, study finds
22.02.2018 | Brown University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Developing reliable quantum computers

International research team makes important step on the path to solving certification problems

Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...

Im Focus: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

Im Focus: Hybrid optics bring color imaging using ultrathin metalenses into focus

For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.

But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...

Im Focus: Stem cell divisions in the adult brain seen for the first time

Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.

The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Stiffness matters

22.02.2018 | Life Sciences

Magnetic field traces gas and dust swirling around supermassive black hole

22.02.2018 | Physics and Astronomy

First evidence of surprising ocean warming around Galápagos corals

22.02.2018 | Earth Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>