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New clue in leukemia mystery: Researchers identify 'poison' employed by deadly enzyme mutations
Date:12/3/2010

thylation from the genome. Interestingly, the researchers also showed that many AML patients have mutations that inactivate TET2, and this causes the same abnormal DNA methylation effect as IDH1 and IDH2 mutations.

"One of the great surprises of this study was that IDH1 and IDH2, which are normally involved in energy metabolism and located far away from DNA and outside of the cell nucleus, could become subverted to make a substance that poisons the genome," says Dr. Ari Melnick, the study's senior author and associate professor of medicine and director of the Raymond and Beverly Sackler Center for Biomedical and Physical Sciences at Weill Cornell Medical College.

"Our study shows for the first time that metabolic enzymes not only help to fuel tumor growth but when mutated can also directly 'rewrite' the instructions that govern the genome," Dr. Melnick continues. One important implication of this work is that it appears technically feasible to create drugs that can specifically stop mutant IDH1 and IDH2 from making the cancer-causing poison. Such inhibitors have the potential to fundamentally restore normal functioning to the genome and thus help to treat leukemias. IDH1 is also frequently mutated in malignant brain tumors, suggesting that the current study has broad implications for several types of cancer.

"These discoveries were only possible thanks to the collaboration of a large team of scientists with expertise in different disciplines from around the world," emphasizes Dr. Melnick, "and thanks to an unusual alliance between multicenter clinical trials groups from Europe and the United States. This spirit of cooperation allowed for the collection and analysis of the massive genomic datasets required for these discoveries to be made. Working together, it will be possible to accelerate the pace of discovery and development of better treatments."


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Contact: Andrew Klein
ank2017@med.cornell.edu
212-821-0560
New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College
Source:Eurekalert

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