DNMT3A review paper AML and CHIP.pdf (2.17 MB)
Epigenetic guardian: a review of the DNA methyltransferase DNMT3A in acute myeloid leukaemia and clonal haematopoiesis
journal contribution
posted on 2023-06-09, 06:24 authored by Sabah Chaudry, Timothy ChevassutTimothy ChevassutAcute myeloid leukaemia (AML) is a haematological malignancy characterized by clonal stem cell proliferation and aberrant block in differentiation. Dysfunction of epigenetic modifiers contributes significantly to the pathogenesis of AML. One frequently mutated gene involved in epigenetic modification is DNMT3A (DNA methyltransferase-3-alpha), a DNA methyltransferase that alters gene expression by de novo methylation of cytosine bases at CpG dinucleotides. Approximately 22% of AML and 36% of cytogenetically normal AML cases carry DNMT3A mutations and around 60% of these mutations affect the R882 codon. These mutations have been associated with poor prognosis and adverse survival outcomes for AML patients. Advances in whole-exome sequencing techniques have recently identified a large number of DNMT3A mutations present in clonal cells in normal elderly individuals with no features of haematological malignancy. Categorically distinct from other preleukaemic conditions, this disorder has been termed clonal haematopoiesis of indeterminate potential (CHIP). Further insight into the mutational landscape of CHIP may illustrate the consequence of particular mutations found in DNMT3A and identify specific “founder” mutations responsible for clonal expansion that may contribute to leukaemogenesis. This review will focus on current research and understanding of DNMT3A mutations in both AML and CHIP.
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Publication status
- Published
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- Published version
Journal
Biomed Research InternationalISSN
2314-6133Publisher
Hindawi Publishing CorporationExternal DOI
Volume
2017Page range
5473197Department affiliated with
- Clinical and Experimental Medicine Publications
Research groups affiliated with
- Haematology Research Group Publications
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- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2017-05-24First Open Access (FOA) Date
2017-05-24First Compliant Deposit (FCD) Date
2017-05-24Usage metrics
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