Metabolic Links to Leukemia

Acute myeloid leukemia linked to metabolite

(RxWiki News) The link between cancer and the body's metabolism is a scientific focus that is bearing more fruit. An "oncometabolite" is cancer-causing metabolite that's involved in the development and progression of cancer.

A new oncometabolite linked to leukemia has been identified.

Scientists have discovered that a mutation in an enzyme involved in metabolism can cause acute myeloid leukemia (AML), a common form of adult leukemia.

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The research team was led by the scientist who discovered oncometabolites - Tak Mak, PhD, at the Princess Margaret Cancer Centre, University Health Network. Researchers from Weill Cornell Medical College and Agios Pharmaceuticals were also involved.

"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," said Dr. Mak, who is the director of The Campbell Family Institute for Breast Cancer Research at Princess Margaret Hospital.

The AML link was found to be metabolite 2-hydroxyglutarate (2HG), which is the by-product of a gene mutation of an enzyme known as isocitrate dehydrogenase (IDH). The IDH gene mutation was first discovered in brain cancers and, later, leukemia.

Working with mice, the team found that this mutation "launches the perfect storm." The oncometabolite sets in motion a wave of activity that crowds out and reduces mature blood cells in the bone marrow, which sets the stage for AML.

"This is one of the most common mutations in AML," said Dr. Mak.  "We also found that it is the common mutation in about 40 percent of a specific type of lymphoma."

Findings from this research were published in the July 3 issue of Nature.

The research was funded by the Canadian Institutes of Health Research, the Ontario Ministry of Health and Long-Term Care and the Terry Fox Foundation. No conflicts of interest were reported.

Review Date: 
July 5, 2012