Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Novel target found for chemotherapy-resistant leukemia cells

13.05.2014

Researchers at Children's Hospital Los Angeles have discovered that by targeting a particular receptor, chemotherapy-resistant cancer cells can be killed in an acute form of childhood leukemia, offering the potential for a future treatment for patients who would otherwise experience relapse of their disease.

Nora Heisterkamp, PhD, and colleagues at The Saban Research Institute of Children's Hospital Los Angeles have discovered that by targeting the B-cell activating receptor (BAFF-R), chemotherapy-resistant precursor B acute lymphoblastic leukemia cells (pre-B ALL) can be selectively killed in vivo and in vitro. Results will be published on May 13 in Molecular Cancer Therapeutics.


This is Nora Heisterkamp, Ph.D.

Credit: Children's Hospital Los Angeles

Acute lymphoblastic leukemia (ALL) is characterized by an excessive amount of white blood cell precursors, called B-cell lymphoblasts, in the blood and bone marrow. B-cell lineage ALL (pre-B ALL) accounts for 80 to 85% of childhood ALL. Although the cure rate has increased, further advances can only be achieved by identifying mechanisms to treat specific subsets of chemotherapy-resistant leukemia cells.

In a previous study (Leukemia, 2013), the researchers had shown that BAFF-R is expressed on pre-B ALL cells but not on their normal counterparts, making selective killing of ALL cells possible by targeting this receptor.

"We've now demonstrated that BAFF-R is a strong potential therapeutic target for treating chemotherapy-resistant leukemia cells, without damaging healthy cells," said Heisterkamp, who is also professor of Research, Pediatrics and Pathology at the Keck School of Medicine of the University of Southern California.

Using a genetically-engineered antibody (anti-BAFF-R monoclonal antibody), Heisterkamp and colleagues have demonstrated that the BAFF-R could be successfully blocked in a dose-dependent manner. Inhibition of BAFF-R function rendered leukemia cells less viable in mouse models of the disease. Also, the presence of this antibody on the pre-B ALL cells resulted in increased killing of the cancer cells by natural killer (NK) cells and macrophages.

"We found that human pre-B ALL cells could be even further reduced when the anti-BAFF-R antibody was combined with chemotherapy or another therapeutic agent," said Heisterkamp. "We are looking at a potential one, two punch." Heisterkamp and her colleagues will continue to evaluate the use of this antibody for the treatment of ALL.

###

Co-authors include Reshmi Parameswaran, Min Lim, Fei Fei, Hisham Abdel-Azim, Anna Arutyunyan, Isabelle Schiffer, John Groffen, of The Saban Research Institute of Children's Hospital Los Angeles; and Margaret E. McLaughlin, Hermann Gram, Heather Huet, of Novartis Institute for Biomedical Research.

Funding for this research came from National Institutes of Health grants PHS CA090321, CA 172040, Alex's Lemonade Stand Foundation for Childhood Cancer, the V-Foundation for Cancer Research and Novartis Pharmaceuticals.

About Children's Hospital Los Angeles

Children's Hospital Los Angeles has been named the best children's hospital in California and among the top five in the nation for clinical excellence with its selection to the prestigious US News & World Report Honor Roll. Children's Hospital is home to The Saban Research Institute, one of the largest and most productive pediatric research facilities in the United States, is one of America's premier teaching hospitals and has been affiliated with the Keck School of Medicine of the University of Southern California since 1932.

For more information, visit http://www.CHLA.org. Follow us on Twitter, Facebook, YouTube and LinkedIn, or visit our blog: http://www.WeTreatKidsBetter.org.

Media Contact: Ellin Kavanagh, ekavanagh@chla.usc.edu (323) 361-8505

Ellin Kavanagh | Eurek Alert!

Further reports about: ALL B-cell Cancer Medicine blood leukemia lymphoblastic receptor therapeutic

More articles from Health and Medicine:

nachricht New concept: Can Resuscitation be delayed?
31.03.2015 | Europäische Akademie Bozen - European Academy Bozen/Bolzano

nachricht For drivers with telescopic lenses, driving experience and training affect road test results
30.03.2015 | Wolters Kluwer Health

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Experiment Provides the Best Look Yet at 'Warm Dense Matter' at Cores of Giant Planets

In an experiment at the Department of Energy's SLAC National Accelerator Laboratory, scientists precisely measured the temperature and structure of aluminum as...

Im Focus: Energy-autonomous and wireless monitoring protects marine gearboxes

The IPH presents a solution at HANNOVER MESSE 2015 to make ship traffic more reliable while decreasing the maintenance costs at the same time. In cooperation with project partners, the research institute from Hannover, Germany, has developed a sensor system which continuously monitors the condition of the marine gearbox, thus preventing breakdowns. Special feature: the monitoring system works wirelessly and energy-autonomously. The required electrical power is generated where it is needed – directly at the sensor.

As well as cars need to be certified regularly (in Germany by the TÜV – Technical Inspection Association), ships need to be inspected – if the powertrain stops...

Im Focus: 3-D satellite, GPS earthquake maps isolate impacts in real time

Method produced by UI researcher could improve reaction time to deadly, expensive quakes

When an earthquake hits, the faster first responders can get to an impacted area, the more likely infrastructure--and lives--can be saved.

Im Focus: Atlantic Ocean overturning found to slow down already today

The Atlantic overturning is one of Earth’s most important heat transport systems, pumping warm water northwards and cold water southwards. Also known as the Gulf Stream system, it is responsible for the mild climate in northwestern Europe. 

Scientists now found evidence for a slowdown of the overturning – multiple lines of observation suggest that in recent decades, the current system has been...

Im Focus: Robot inspects concrete garage floors and bridge roadways for damage

Because they are regularly subjected to heavy vehicle traffic, emissions, moisture and salt, above- and underground parking garages, as well as bridges, frequently experience large areas of corrosion. Most inspection systems to date have only been capable of inspecting smaller surface areas.

From April 13 to April 17 at the Hannover Messe (hall 2, exhibit booth C16), engineers from the Fraunhofer Institute for Nondestructive Testing IZFP will be...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

World Conference On Regenerative Medicine 2015: Registration And Abstract Submission Now Open

25.03.2015 | Event News

University presidents from all over the world meet in Hamburg

19.03.2015 | Event News

10. CeBiTec Symposium zum Big Data-Problem

17.03.2015 | Event News

 
Latest News

Biology in a twist -- deciphering the origins of cell behavior

31.03.2015 | Life Sciences

Wrapping carbon nanotubes in polymers enhances their performance

31.03.2015 | Materials Sciences

Research Links Two Millennia of Cyclones, Floods, El Niño

31.03.2015 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>