Epigenetic changes
In addition to genetic alterations, it is becoming increasingly apparent that epigenetic changes can also influence the development and progression of myeloma.
Epigenetics refers to the external modifications to DNA that turn genes on and off. These modifications do not involve changes to the underlying DNA but instead affect the structure of genes and how they are regulated or the way they function. Epigenetic change is a regular and natural event but can be influenced by several factors including age, environment/lifestyle and disease state.
In myeloma, at least three epigenetic systems are thought to be affected which lead to changes in the expression and/or function of genes involved in the control of the cell cycle, survival and cell death pathways, including during B cell differentiation and maturation. These include:
- DNA methylation (turning genes off)
- Histone modification (affecting DNA packaging and therefore turning genes on or off)
- Non-coding RNA expression (involved in silencing genes)
By understanding more about which epigenetic changes contribute to the pathogenesis of myeloma and in fact, some of the associated complications such as myeloma bone disease, the hope is new therapeutic targets may be identified.