Acute myeloid leukemia (AML), a type of blood cancer, is characterized by an increase in the number of abnormal white blood cells in the bone marrow, frequently causing hematopoietic insufficiency. It is a heterogeneous disease featuring cytogenetic aberrations, recurrent somatic mutations and alterations in gene expression. DNA (cytosine-5-)-methyltransferase 3 alpha (DNMT3A) is closely associated with epigenetic modifications in mammalian development and disease. More recent studies have identified recurrent somatic mutations in DNMT3A in AML, most of which are heterozygous. The DNMT3A R882 codon is a mutational hotspot. The frequency of DNMT3A mutations varies among different countries, but mutations have been found to be associated with cytogenetics, age, white blood cell (WBC) count, prognosis and response of patients to chemotherapy. The normal function of DNMT3A can be disrupted by these mutations, which subsequently results in an abnormality of epigenetic modification. These data suggest that mutations in the DNMT3A gene represent a novel class of mutations in AML with distinct biological and clinical features. Further studies are needed to elucidate the exact molecular mechanism and function of DNMT3A mutations in leukemogenesis.
Keywords: Acute myeloid leukemia (AML); DNA (cytosine-5-)-methyltransferase 3 alpha (DNMT3A); epigenetic modification; somatic mutation.