4.5 Review

Decoding DNA methylation in epigenetics of multiple myeloma

Journal

BLOOD REVIEWS
Volume 51, Issue -, Pages -

Publisher

CHURCHILL LIVINGSTONE
DOI: 10.1016/j.blre.2021.100872

Keywords

DNA methylation; Epigenetic modifier; DNMT; TET; Multiple myeloma

Categories

Funding

  1. National Natural Science Foundation of China [81471165, 81670190, 81671108, 81670189, 81870160]
  2. Natural Science Foundation of the Jilin Province [20190201042JC, 20190201163JC, 20180520114JH, 20200201550JC]
  3. Health and Family Planning Commission of Jilin Province [2017Q027]

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This article reviews the alterations in DNA methylome and DNA methylation modifiers in multiple myeloma (MM), with a focus on DNA methyltransferases (DNMTs) and tet methylcytosine dioxygenases (TETs). The authors discuss the regulation and function of these DNA methylation modifiers in MM cells, providing a rationale for the development of novel epigenetic therapies targeting DNA methylation in MM.
Dysregulation of DNA methylation in B cells has been observed during their neoplastic transformation and therefore closely associated with various B-cell malignancies including multiple myeloma (MM), a malignancy of terminally differentiated plasma cells. Emerging evidence has unveiled pronounced alterations in DNA methylation in MM, including both global and gene-specific changes that can affect genome stability and gene transcription. Moreover, dysregulated expression of DNA methylation-modifying enzymes has been related with myelomagenesis, disease progression, and poor prognosis. However, the functional roles of the epigenetic abnormalities involving DNA methylation in MM remain elusive. In this article, we review current understanding of the alterations in DNA methylome and DNA methylation modifiers in MM, particularly focusing on DNA methyltransferases (DNMTs) and tet methylcytosine dioxygenases (TETs). We also discuss how these DNA methylation modifiers may be regulated and function in MM cells, therefore providing a rationale for developing novel epigenetic therapies targeting DNA methylation in MM.

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