Epigenetics of Multiple Myeloma Bone Disease View Full Text


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Article Info

DATE

2019-02-09

AUTHORS

Sree H Pulugulla, Juraj Adamik

ABSTRACT

Multiple myeloma bone disease (MMDB) is a devastating clinical manifestation of multiple myeloma associated with excessive bone osteolysis, which results from enhanced osteoclastogenesis and suppression of bone marrow stromal cell (BMSC) differentiation into osteoblasts. Impaired osteogenesis and functional alterations of myeloma-exposed BMSCs (MM-BMSCs) during the course of disease evolution significantly contribute to myeloma growth, metastasis, and chemoresistance. This review highlights new studies demonstrating that epigenetic modalities including chromatin-mediated gene silencing and non-coding RNA contribute to pathogenesis of MM-BMSCs. Inhibitors targeting histone-modifying enzymes EZH2, JMJD3, HDACs, and BET proteins have been successfully used to revert osteogenic suppression of MM-BMSCs. Aberrant expression of non-coding RNA cause functional changes associated with senescence, osteogenic suppression, and tumor-promoting phenotype of MM-BMSCs. Epigenetic events guiding transformations of the surrounding BMSC compartments are ultimately linked to disease onset and progression and open new therapeutic opportunity to target dissemination of MM tumors and reliably repair bone lesions. More... »

PAGES

1-11

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s40610-019-0117-2

DOI

http://dx.doi.org/10.1007/s40610-019-0117-2

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1112041336


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