Featured Research

from universities, journals, and other organizations

Key pathway implicated in progression of childhood cancer identified

Date:
September 13, 2010
Source:
NYU Langone Medical Center / New York University School of Medicine
Summary:
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. 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.

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.


Story Source:

The above story is based on materials provided by NYU Langone Medical Center / New York University School of Medicine. Note: Materials may be edited for content and length.


Journal Reference:

  1. Lluis Espinosa, Severine Cathelin, Teresa D'Altri, Thomas Trimarchi, Alexander Statnikov, Jordi Guiu, Veronica Rodilla, Julia Inglιs-Esteve, Josep Nomdedeu, Beatriz Bellosillo, Carles Besses, Omar Abdel-Wahab, Nicole Kucine, Shao-Cong Sun, Guangchan Song, Charles C. Mullighan, Ross L. Levine, Klaus Rajewsky, Iannis Aifantis, Anna Bigas. The Notch/Hes1 Pathway Sustains NF-κB Activation through CYLD Repression in T Cell Leukemia. Cancer Cell, 2010; 18 (3): 268-281 DOI: 10.1016/j.ccr.2010.08.006

Cite This Page:

NYU Langone Medical Center / New York University School of Medicine. "Key pathway implicated in progression of childhood cancer identified." ScienceDaily. ScienceDaily, 13 September 2010. <www.sciencedaily.com/releases/2010/09/100913121658.htm>.
NYU Langone Medical Center / New York University School of Medicine. (2010, September 13). Key pathway implicated in progression of childhood cancer identified. ScienceDaily. Retrieved September 1, 2014 from www.sciencedaily.com/releases/2010/09/100913121658.htm
NYU Langone Medical Center / New York University School of Medicine. "Key pathway implicated in progression of childhood cancer identified." ScienceDaily. www.sciencedaily.com/releases/2010/09/100913121658.htm (accessed September 1, 2014).

Share This




More Health & Medicine News

Monday, September 1, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

We've Got Mites Living In Our Faces And So Do You

We've Got Mites Living In Our Faces And So Do You

Newsy (Aug. 30, 2014) — A new study suggests 100 percent of adult humans (those over 18 years of age) have Demodex mites living in their faces. Video provided by Newsy
Powered by NewsLook.com
Liberia Continues Fight Against Ebola

Liberia Continues Fight Against Ebola

AFP (Aug. 30, 2014) — Authorities in Liberia try to stem the spread of the Ebola epidemic by raising awareness and setting up sanitation units for people to wash their hands. Duration: 00:41 Video provided by AFP
Powered by NewsLook.com
California Passes 'yes-Means-Yes' Campus Sexual Assault Bill

California Passes 'yes-Means-Yes' Campus Sexual Assault Bill

Reuters - US Online Video (Aug. 30, 2014) — California lawmakers pass a bill requiring universities to adopt "affirmative consent" language in their definitions of consensual sex, part of a nationwide drive to curb sexual assault on campuses. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
New Drug Could Reduce Cardiovascular Deaths

New Drug Could Reduce Cardiovascular Deaths

Newsy (Aug. 30, 2014) — The new drug from Novartis could reduce cardiovascular deaths by 20 percent compared to other similar drugs. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins