Epigenetic guardian: a review of the DNA methyltransferase DNMT3A in acute myeloid leukaemia and clonal haematopoiesis

Chaudry, Sabah and Chevassut, Timothy (2017) Epigenetic guardian: a review of the DNA methyltransferase DNMT3A in acute myeloid leukaemia and clonal haematopoiesis. Biomed Research International, 2017. p. 5473197. ISSN 2314-6133

[img] PDF - Published Version
Available under License Creative Commons Attribution.

Download (2MB)

Abstract

Acute 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.

Item Type: Article
Schools and Departments: Brighton and Sussex Medical School > Brighton and Sussex Medical School
Subjects: R Medicine
R Medicine > RC Internal medicine
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology Including cancer and carcinogens
Depositing User: Timothy Chevassut
Date Deposited: 24 May 2017 15:18
Last Modified: 24 May 2017 16:04
URI: http://sro.sussex.ac.uk/id/eprint/68223

View download statistics for this item

📧 Request an update