DNMT3A Gene

The DNMT3A gene (DNMT3A is the acronym for "DNA Methyltransferase 3 alpha") is a protein-coding gene located on chromosome 2p23.3. The DNMT3A gene encodes a DNA methyltransferase. The protein is localized in the cytoplasm and nucleus.

DNMT3A is one of several epigenetic modifiers that are consistently mutated in acute myeloid leukemia (AML). In the past, the prognostic significance of epigenetic modifying genes (DNMT3A, TET2 and IDH1/2) in patients with acute myeloid leukemia (AML) has been extensively studied. In larger studies, the prevalence rates for the mutations were shown to be as follows (Ahn JS et al. 2016):

• FLT3-ITD positivity(FLT3-ITD(pos)) (32,2%)
• NPM1 mutation(43.5%)
• CEBPA mutation (double) (24.6%)
• DNMT3A mutation (DNMT3A(mut)) (31,3%)
• DNMT3A R882(mut) (18.3%)
• TET2 mutation (8.7%)
• IDH1/IDH2 mutation(16.5%).

The 5-year overall survival (OS) and event-free survival (EFS) rates revealed unfavorable prognostic factors for FLT3-ITD, DNMT3A R882 for OS. In addition, both mutations were significant risk factors for EFS and relapse (Ahn JS et al. 2016).

Diseases associated with DNMT3A include:

• Tatton-Brown-Rahman syndrome and
• Heyn-Sproul-Jackson syndrome.

An important paralogue of this gene is DNMT3B.

1. Kumar D et al (2018) DNMT3A (R882) mutation features and prognostic effect in acute myeloid leukemia in Coexistent with NPM1 and FLT3 mutations. Hematol Oncol Stem Cell Ther 11:82-89.
2. Ahn JS et al (2016) DNMT3A R882 Mutation with FLT3-ITD Positivity Is an Extremely Poor Prognostic Factor in Patients with Normal-Karyotype Acute Myeloid Leukemia after Allogeneic Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant 22:61-70.