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Epigenetics of Multiple Myeloma Bone Disease

  • Sree H Pulugulla
  • Juraj AdamikEmail author
Molecular Biology of Bone Metastasis (H Taipaleenmäki and M Capulli, Section Editors)
  • 6 Downloads
Part of the following topical collections:
  1. Topical Collection on Molecular Biology of Bone Metastasis

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.

Keywords

Multiple myeloma bone disease Epigenetics Chromatin regulation Histone modifiers Non-coding RNA Bone marrow mesenchymal stromal cells 

Notes

Compliance with Ethical Standards

Conflict of Interest

The authors do not have potential conflict of interest that impacts this manuscript.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Biological SciencesDuquesne UniversityPittsburghUSA
  2. 2.Division of Hematology-Oncology, UPMC Hillman Cancer CenterUniversity of Pittsburgh School of MedicinePittsburghUSA

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