The azanucleosides decitabine and azacytidine are used widely in the treatment of myeloid
neoplasia and increasingly in the context of combination therapies. Although they were long regarded
as being largely interchangeable in their function as hypomethylating agents, the azanucleosides
actually have different mechanisms of action; decitabine interferes primarily with the methylation
of DNA and azacytidine with that of RNA. Here, we examine the role of DNA methylation in the
lineage commitment of stem cells during normal hematopoiesis and consider how mutations in
epigenetic regulators such as DNMT3A and TET2 can lead to clonal expansion and subsequent
neoplastic progression. We also consider why the efficacy of azanucleoside treatment is not limited to
neoplasias carrying mutations in epigenetic regulators. Finally, we summarise recent data describing
a role for azacytidine-sensitive RNA methylation in lineage commitment and in the cellular response
to stress. By summarising and interpreting evidence for azanucleoside involvement in a range of
cellular processes, our review is intended to illustrate the need to consider multiple modes of action
in the design and stratification of future combination therapies.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:88485 |
| Date | 06 December 2023 |
| Creators | Stein, Anna, Platzbecker, Uwe, Cross, Michael |
| Publisher | MDPI |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 2073-4409, 10.3390/cells11162589 |
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