Called an "oncometabolite" for its role in cancer metabolism, the metabolite2-hydroxyglutarate (2HG) is a by-product of a gene mutation of an enzyme known as isocitrate dehydrogenase (IDH).
Says Dr. Tak Mak of the findings published today in Nature: "For the first time, we have demonstrated how a metabolite can cause cancer. This sets the stage for developing inhibitors to block the mutation and prevent the production of this disease-initiating enzyme." The research team included scientists at Weill Cornell Medical College, New York City, and Agios Pharmaceuticals, Cambridge, Massachusetts.
Dr. Mak, Director, The Campbell Family Institute for Breast Cancer Research at Princess Margaret Hospital, is an internationally acclaimed immunologist renowned for his 1984 discovery of cloning the human T-cell receptor. He is also Professor, University of Toronto, in the Departments of Medical Biophysics and Immunology.
The connection between cancer and metabolism has fascinated scientists at Agios and Dr. Mak, who were the first to identify the oncometabolite in research published in Nature (2009) and The Journal of Experimental Medicine (2010). The IDH gene mutation was initially discovered in brain cancers in 2008 by American scientists at Johns Hopkins in Baltimore and subsequently also linked to leukemia.
In the lab, Dr. Mak's team genetically engineered a mouse model with the mutation in its blood system to mimic human AML. They discovered that the gene mutation launches the perfect storm for the oncometabolite to trigger the blood system to increase the stem cells pool and reduce mature blood cells in the bone marrow. The resulting condition creates a situation with similarities to myelodysplastic syndrome – one of the precursors to this type of leukemia.
"This is one of the most common mutations in AML," says Dr. Mak. "We also found that it is the common mutation in about 40% of a specific type of lymphoma." The mutation is also known to be involved in about 70-90% of low-grade brain cancers (glioblastomas gliomas) and a variety of other cancers.
About the Princess Margaret Cancer Centre, University Health Network
Princess Margaret Hospital and Ontario Cancer Institute, the hospital's research arm, have achieved an international reputation as global leaders in the fight against cancer. The Princess Margaret Cancer Centre is part of University Health Network, which also includes Toronto General Hospital, Toronto Western Hospital and Toronto Rehabilitation Institute. All are research hospitals affiliated with the University of Toronto. For more information, go to www.theprincessmargaret.ca or www.uhn.ca
Jane Finlayson | EurekAlert!
New way to look at cell membranes could change the way we study disease
19.11.2018 | University of Oxford
Controlling organ growth with light
19.11.2018 | European Molecular Biology Laboratory
Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.
Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...
Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.
Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...
Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.
In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...
On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.
When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure
Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...
19.11.2018 | Event News
09.11.2018 | Event News
06.11.2018 | Event News
19.11.2018 | Materials Sciences
19.11.2018 | Information Technology
19.11.2018 | Life Sciences