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Epigenetics of Multiple Myeloma Bone Disease

  • Molecular Biology of Bone Metastasis (H Taipaleenmäki and M Capulli, Section Editors)
  • Published:
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Abstract

Purpose of Review

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.

Recent Findings

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.

Summary

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.

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Authors and Affiliations

  1. Department of Biological Sciences, Duquesne University, 201 Melon Hall, Pittsburgh, PA, 15219, USA

    Sree H Pulugulla

  2. Division of Hematology-Oncology, UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Suite 1.20, 5117 Centre Avenue, Pittsburgh, PA, 15213, USA

    Juraj Adamik

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  1. Sree H Pulugulla
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This article is part of the Topical Collection on Molecular Biology of Bone Metastasis

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Pulugulla, S.H., Adamik, J. Epigenetics of Multiple Myeloma Bone Disease. Curr Mol Bio Rep 5, 86–96 (2019). https://doi.org/10.1007/s40610-019-0117-2

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