DNMT3A and acute myeloid leukemia: DNMT3A mutations are among the most common alterations in AML, just behind FLT3/ITD.[1, 2, 7] While AML-associated mutations have been identified throughout the body of the gene, the overwhelming majority are heterozygous missense mutations within the catalytic domain, often affecting Arginine 882.[8] In vitro studies suggest the R882H mutation leads to reduced methyltransferase activity, and acts in a dominant negative manner by impairing tetramer formation.[9–11]