DNMT3A mutations in acute myeloid leukemia
Abstract
Abstract
Acute myeloid leukemia (AML) is a heterogeneous disease affecting pluripotent stem cells and characterized by ineffective hematopoiesis. In the last years, progresses in molecular technologies lead to identification of numerous gene mutations, which providing more complete insight in oncogenic events and allow to optimize risk stratification of AML patients. Moreover, definition of particular mutations allows personalized approaches to treatments that are based on an individual mutation profiles. More recently, a new class of mutations affecting genes for DNA methylation and post-translational histone modification was identified in AML.
These mutations frequently occur in the DNA nucleotide methyltransferase 3A gene (DNMT3A). DNMT3A belongs to the mammalian methyltransferase gene family that is responsible for tissue-specific gene expression. DNMT3A plays an important role in epigenetically regulated gene expression and repression. DNMT3A mutations represent a potential target in the pathogenesis of AML. The likely mechanism by which DNMT3A loss contributes to leukemogenesis is altered DNA methylation and the attendant gene expression changes. There are evidence that DNMT3A mutation are present in the early pre-leukemic cells, and seems to be a “founder” mutation, which can be implicated as functional components of AML evolution.
Different studies have shown a negative impact of DNMT3A mutations on outcomes in patients with AML. Prognostic effect is known to depend on certain biological factors as well as a combination of cytogenetics and other mutations.
In this review we address the biological features of DNMT3A gene, clinical and prognostic impact of DNMT3A, and therapeutic options.
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DOI: http://dx.doi.org/10.18103/imr.v2i9.172
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