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Published on: July 15, 2015
The biological significance of histone modifiers in multiple myeloma: clinical applications
Hiroto Ohguchi1,2, Teru Hideshima3, Kenneth C Anderson4
1Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. ohguchi@kumamoto-u.ac.jp.
Abstract:
Multiple myeloma (MM) is a clonal plasma cell disorder that is characterized by a variety of genetic alterations. Recent studies have highlighted not only the importance of these genetic events but also epigenetic aberrations including DNA methylation, histone modifications, and non-coding RNAs in the biology of MM. Post-translational modifications of histone, such as methylation and acetylation, contribute to chromatin dynamics, and are modulated by histone modifying enzymes, and dysregulation of these enzymes is implicated in the pathogenesis of cancers, including MM. Histone modifiers also have non-histone substrates and enzymatically independent roles, which are also involved in tumorigenesis. Here we review and provide comprehensive insight into the biologic significance of histone methyl- and acetyl-modifiers in MM, and further provide an overview of the clinical applications of histone modifier inhibitors, especially histone deacetylase inhibitors. These findings underline the emerging roles of histone modifiers in the pathogenesis of MM, and further highlight the possibility of novel epigenetic therapies in MM.
Insights
Histone modifiers play crucial roles in multiple myeloma (MM) pathogenesis through epigenetic changes. Inhibitors targeting these histone modifiers show promise for novel epigenetic therapies in MM treatment.
Area of Science:
- Oncology
- Epigenetics
- Molecular Biology
Background:
- Multiple myeloma (MM) is a plasma cell cancer driven by genetic and epigenetic alterations.
- Histone modifications, regulated by histone modifying enzymes, are critical for chromatin dynamics and cancer development.
- Dysregulation of histone modifying enzymes and their non-histone roles contribute to MM pathogenesis.
Purpose of the Study:
- To review the biological significance of histone methyl- and acetyl-modifiers in MM.
- To provide an overview of the clinical applications of histone modifier inhibitors in MM.
Main Methods:
- Comprehensive literature review of histone modifiers in multiple myeloma.
- Analysis of epigenetic aberrations including DNA methylation, histone modifications, and non-coding RNAs in MM.
- Examination of the roles of histone modifying enzymes and their inhibitors.
Main Results:
- Histone methyl- and acetyl-modifiers are significantly involved in the pathogenesis of MM.
- Histone modifiers possess enzymatically independent roles contributing to tumorigenesis.
- Histone deacetylase inhibitors represent a key clinical application in MM epigenetic therapy.
Conclusions:
- Histone modifiers are emerging as critical players in MM development.
- Targeting histone modifiers offers a promising avenue for novel epigenetic therapies in MM.
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