DNMT3A in haematological malignancies

Nat Rev Cancer. 2015 Mar;15(3):152-65. doi: 10.1038/nrc3895. Epub 2015 Feb 19.

Abstract

DNA methylation patterns are disrupted in various malignancies, suggesting a role in the development of cancer, but genetic aberrations directly linking the DNA methylation machinery to malignancies were rarely observed, so this association remained largely correlative. Recently, however, mutations in the gene encoding DNA methyltransferase 3A (DNMT3A) were reported in patients with acute myeloid leukaemia (AML), and subsequently in patients with various other haematological malignancies, pointing to DNMT3A as a critically important new tumour suppressor. Here, we review the clinical findings related to DNMT3A, tie these data to insights from basic science studies conducted over the past 20 years and present a roadmap for future research that should advance the agenda for new therapeutic strategies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • DNA (Cytosine-5-)-Methyltransferases / genetics*
  • DNA Methylation*
  • Gene Expression Regulation, Neoplastic / genetics*
  • Hematologic Neoplasms / genetics*
  • Humans
  • Leukemia, Myeloid, Acute / genetics
  • Mutation
  • Prognosis

Substances

  • DNA (Cytosine-5-)-Methyltransferases
  • DNA methyltransferase 3A