Scientists link 'oncometabolite' to onset of acute myeloid leukemia

July 4, 2012

A team of international scientists led by principal investigator Dr. Tak Mak at the Princess Margaret Cancer Centre, University Health Network, has identified a causative link between the product of a mutated metabolic enzyme and the onset of acute myeloid leukemia (AML), one of the most common types of leukemia in adults.

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 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 (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 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.

Dr. Mak's interest in the blood system began as a young researcher three decades ago with Drs. Ernest McCulloch and James Till, the acclaimed "fathers of stem cell science" at Ontario Cancer Institute, the research arm of Princess Margaret Hospital, whose 1961 discovery of stem cells launched the new field.

Explore further: Cancer scientists discover new way breast cancer cells adapt to environmental stress

Related Stories

Cancer scientists discover new way breast cancer cells adapt to environmental stress

May 15, 2011
An international research team led by Dr. Tak Mak, Director, The Campbell Family Institute for Breast Cancer Research at Princess Margaret Hospital (PMH), has discovered a new aspect of "metabolic transformation", the process ...

Clinical importance of leukemia stem cells validated

August 28, 2011
Cancer scientists have long debated whether all cells within a tumour are equal or whether some cancer cells are more potent - a question that has been highly investigated in experimental models in the last decade. Research ...

Gene mutation contributes to leukemia by enhancing function of blood stem cells

July 1, 2011
Researchers at Memorial Sloan-Kettering Cancer Center and New York University have discovered how a mutation in the gene known as TET2 contributes to the development of some leukemias. When a mutation in TET2 occurs, it enhances ...

Recommended for you

Clinical trial suggests new cell therapy for relapsed leukemia patients

November 20, 2017
A significant proportion of children and young adults with treatment-resistant B-cell leukemia who participated in a small study achieved remission with the help of a new form of gene therapy, according to researchers at ...

Cell-weighing method could help doctors choose cancer drugs

November 20, 2017
Doctors have many drugs available to treat multiple myeloma, a type of blood cancer. However, there is no way to predict, by genetic markers or other means, how a patient will respond to a particular drug. This can lead to ...

Lung cancer triggers pulmonary hypertension

November 17, 2017
Shortness of breath and respiratory distress often increase the suffering of advanced-stage lung cancer patients. These symptoms can be triggered by pulmonary hypertension, as scientists at the Max Planck Institute for Heart ...

Researchers discover an Achilles heel in a lethal leukemia

November 16, 2017
Researchers have discovered how a linkage between two proteins in acute myeloid leukemia enables cancer cells to resist chemotherapy and showed that disrupting the linkage could render the cells vulnerable to treatment. St. ...

Computer program finds new uses for old drugs

November 16, 2017
Researchers at the Case Comprehensive Cancer Center at Case Western Reserve University School of Medicine have developed a computer program to find new indications for old drugs. The computer program, called DrugPredict, ...

Pharmacoscopy improves therapy for relapsed blood cancer in a first clinical trial

November 16, 2017
Researchers at CeMM and the Medical University of Vienna presented a preliminary report in The Lancet Hematology on the clinical impact of an integrated ex vivo approach called pharmacoscopy. The procedures measure single-cell ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.