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!
Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory
Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP
Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.
Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
09.12.2016 | Life Sciences
09.12.2016 | Ecology, The Environment and Conservation
09.12.2016 | Health and Medicine