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.