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Epigenetic Changes in Neoplastic Mast Cells and Potential Impact in Mastocytosis

期刊

出版社

MDPI
DOI: 10.3390/ijms22062964

关键词

mastocytosis; epigenetics; DNA methylation; demethylating agents; DNMT3A; TET2; microRNA

资金

  1. Polpharma Scientific Foundation, Poland [07-0045]
  2. Polish Ministry of Science and Higher Education [ST 02-0141/07/231, ST 02-0066/07/253]
  3. project 14.5 by Nofer Institute of Occupational Medicine, Lodz, Poland
  4. Austrian Science Fund (FWF) [P32470-B, F4704-B20]

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This article provides an overview of epigenetic changes relevant to systemic mastocytosis, including gene mutations and methylation patterns, as well as discussing pathways and events triggering disease progression. Additionally, the effects of epigenetic targets and drugs on neoplastic mast cells are explored.
Systemic mastocytosis (SM) is a hematologic neoplasm with abnormal accumulation of mast cells in various organ systems such as the bone marrow, other visceral organs and skin. So far, only little is known about epigenetic changes contributing to the pathogenesis of SM. In the current article, we provide an overview of epigenetic changes that may occur and be relevant to mastocytosis, including mutations in genes involved in epigenetic processes, such as TET2, DNMT3A and ASXL1, and global and gene-specific methylation patterns in neoplastic cells. Moreover, we discuss methylation-specific pathways and other epigenetic events that may trigger disease progression in mast cell neoplasms. Finally, we discuss epigenetic targets and the effects of epigenetic drugs, such as demethylating agents and BET-targeting drugs, on growth and viability of neoplastic mast cells. The definitive impact of these targets and the efficacy of epigenetic therapies in advanced SM need to be explored in future preclinical studies and clinical trials.

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