A massive accumulation of DNA methylation causes genes to function abnormally, resulting in acute myelogenous leukemia (AML) when enzyme mutations generate a chemical “poison” that prevents the removal of the methylation genomes.
This unexpected cancer-causing mechanism came to light during an international research team’s search for chemical clues as to how leukemia arises from normal bone marrow cells. In analyzing the genomes of 750 patients in the United States and Europe with AML, the scientists discovered the unique chemical signature in the genomes of patients with mutations in the enzymes IDH1 or IDH2, which occur frequently in AML.
“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,” noted senior author Ari Melnick, MD, of Weill Cornell Medical College, in a statement highlighting the findings. According to Dr. Melnick, this could mean that drugs could be created to stop mutant IDH1 and IDH2 from making the cancer-causing poison and potentially restore normal functioning to the genome, thus helping to treat the leukemia and perhaps other types of cancers as well.
Dr. Melnick and colleagues describe their findings in the journal Cancer Cell (http://download.cell.com/cancer-cell/pdf/PIIS1535610810004836.pdf?intermediate=true).