Exome sequencing acute monocytic leukemia

Sequencing of the exomes―the coding part of DNA―of individuals with acute monocytic leukemia (AML-M5), a subtype of acute myeloid leukemia, is reported this week in Nature Genetics. This study suggests a role for epigenetic changes and altered DNA methyltransferase activity in the pathogenesis of AML. Zhu Chen and colleagues report the sequencing of exomes of nine AML-M5 cases. They identified 66 leukemia-specific alterations in 63 genes, and genotyped these changes in 98 additional cases. They identified recurrent mutations in DNMT3A, which encodes a DNA methyltransferase, in 20.5% of cases. They find that the enzymatic activity of the mutant DNMT3A was reduced in vitro, and samples carrying these mutations showed up-regulation of expression of genes that may be targets of DNMT3A.