The Epigenome in Multiple Myeloma: Impact on Tumor Cell Plasticity and Drug Response
Multiple myeloma (MM) is a clonal plasma cell malignancy that develops primarily in the bone marrow (BM), where reciprocal interactions with the BM niche foster MM cell survival, growth, and drug resistance. MM cells furthermore reshape the BM to their own needs by affecting the different BM stromal...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2018-12-01
|
Series: | Frontiers in Oncology |
Subjects: | |
Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2018.00566/full |
id |
doaj-5a2cfc2b96a4459598b5c584e31de1ec |
---|---|
record_format |
Article |
spelling |
doaj-5a2cfc2b96a4459598b5c584e31de1ec2020-11-24T20:43:30ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2018-12-01810.3389/fonc.2018.00566428402The Epigenome in Multiple Myeloma: Impact on Tumor Cell Plasticity and Drug ResponseEva De Smedt0Hui Lui1Hui Lui2Ken Maes3Kim De Veirman4Eline Menu5Karin Vanderkerken6Elke De Bruyne7Department of Hematology and Immunology-Myeloma Center Brussels, Vrije Universiteit Brussel, Brussels, BelgiumDepartment of Hematology and Immunology-Myeloma Center Brussels, Vrije Universiteit Brussel, Brussels, BelgiumDepartment of Hematology, Tianjin Medical University General Hospital, Tianjin, ChinaDepartment of Hematology and Immunology-Myeloma Center Brussels, Vrije Universiteit Brussel, Brussels, BelgiumDepartment of Hematology and Immunology-Myeloma Center Brussels, Vrije Universiteit Brussel, Brussels, BelgiumDepartment of Hematology and Immunology-Myeloma Center Brussels, Vrije Universiteit Brussel, Brussels, BelgiumDepartment of Hematology and Immunology-Myeloma Center Brussels, Vrije Universiteit Brussel, Brussels, BelgiumDepartment of Hematology and Immunology-Myeloma Center Brussels, Vrije Universiteit Brussel, Brussels, BelgiumMultiple myeloma (MM) is a clonal plasma cell malignancy that develops primarily in the bone marrow (BM), where reciprocal interactions with the BM niche foster MM cell survival, growth, and drug resistance. MM cells furthermore reshape the BM to their own needs by affecting the different BM stromal cell types resulting in angiogenesis, bone destruction, and immune suppression. Despite recent advances in treatment modalities, MM remains most often incurable due to the development of drug resistance to all standard of care agents. This underscores the unmet need for these heavily treated relapsed/refractory patients. Disruptions in epigenetic regulation are a well-known hallmark of cancer cells, contributing to both cancer onset and progression. In MM, sequencing and gene expression profiling studies have also identified numerous epigenetic defects, including locus-specific DNA hypermethylation of cancer-related and B cell specific genes, genome-wide DNA hypomethylation and genetic defects, copy number variations and/or abnormal expression patterns of various chromatin modifying enzymes. Importantly, these so-called epimutations contribute to genomic instability, disease progression, and a worse outcome. Moreover, the frequency of mutations observed in genes encoding for histone methyltransferases and DNA methylation modifiers increases following treatment, indicating a role in the emergence of drug resistance. In support of this, accumulating evidence also suggest a role for the epigenetic machinery in MM cell plasticity, driving the differentiation of the malignant cells to a less mature and drug resistant state. This review discusses the current state of knowledge on the role of epigenetics in MM, with a focus on deregulated histone methylation modifiers and the impact on MM cell plasticity and drug resistance. We also provide insight into the potential of epigenetic modulating agents to enhance clinical drug responses and avoid disease relapse.https://www.frontiersin.org/article/10.3389/fonc.2018.00566/fullmultiple myelomaepigeneticshistone methyltransferaseshistone demethylasesMM cell plasticitydrug response |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Eva De Smedt Hui Lui Hui Lui Ken Maes Kim De Veirman Eline Menu Karin Vanderkerken Elke De Bruyne |
spellingShingle |
Eva De Smedt Hui Lui Hui Lui Ken Maes Kim De Veirman Eline Menu Karin Vanderkerken Elke De Bruyne The Epigenome in Multiple Myeloma: Impact on Tumor Cell Plasticity and Drug Response Frontiers in Oncology multiple myeloma epigenetics histone methyltransferases histone demethylases MM cell plasticity drug response |
author_facet |
Eva De Smedt Hui Lui Hui Lui Ken Maes Kim De Veirman Eline Menu Karin Vanderkerken Elke De Bruyne |
author_sort |
Eva De Smedt |
title |
The Epigenome in Multiple Myeloma: Impact on Tumor Cell Plasticity and Drug Response |
title_short |
The Epigenome in Multiple Myeloma: Impact on Tumor Cell Plasticity and Drug Response |
title_full |
The Epigenome in Multiple Myeloma: Impact on Tumor Cell Plasticity and Drug Response |
title_fullStr |
The Epigenome in Multiple Myeloma: Impact on Tumor Cell Plasticity and Drug Response |
title_full_unstemmed |
The Epigenome in Multiple Myeloma: Impact on Tumor Cell Plasticity and Drug Response |
title_sort |
epigenome in multiple myeloma: impact on tumor cell plasticity and drug response |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Oncology |
issn |
2234-943X |
publishDate |
2018-12-01 |
description |
Multiple myeloma (MM) is a clonal plasma cell malignancy that develops primarily in the bone marrow (BM), where reciprocal interactions with the BM niche foster MM cell survival, growth, and drug resistance. MM cells furthermore reshape the BM to their own needs by affecting the different BM stromal cell types resulting in angiogenesis, bone destruction, and immune suppression. Despite recent advances in treatment modalities, MM remains most often incurable due to the development of drug resistance to all standard of care agents. This underscores the unmet need for these heavily treated relapsed/refractory patients. Disruptions in epigenetic regulation are a well-known hallmark of cancer cells, contributing to both cancer onset and progression. In MM, sequencing and gene expression profiling studies have also identified numerous epigenetic defects, including locus-specific DNA hypermethylation of cancer-related and B cell specific genes, genome-wide DNA hypomethylation and genetic defects, copy number variations and/or abnormal expression patterns of various chromatin modifying enzymes. Importantly, these so-called epimutations contribute to genomic instability, disease progression, and a worse outcome. Moreover, the frequency of mutations observed in genes encoding for histone methyltransferases and DNA methylation modifiers increases following treatment, indicating a role in the emergence of drug resistance. In support of this, accumulating evidence also suggest a role for the epigenetic machinery in MM cell plasticity, driving the differentiation of the malignant cells to a less mature and drug resistant state. This review discusses the current state of knowledge on the role of epigenetics in MM, with a focus on deregulated histone methylation modifiers and the impact on MM cell plasticity and drug resistance. We also provide insight into the potential of epigenetic modulating agents to enhance clinical drug responses and avoid disease relapse. |
topic |
multiple myeloma epigenetics histone methyltransferases histone demethylases MM cell plasticity drug response |
url |
https://www.frontiersin.org/article/10.3389/fonc.2018.00566/full |
work_keys_str_mv |
AT evadesmedt theepigenomeinmultiplemyelomaimpactontumorcellplasticityanddrugresponse AT huilui theepigenomeinmultiplemyelomaimpactontumorcellplasticityanddrugresponse AT huilui theepigenomeinmultiplemyelomaimpactontumorcellplasticityanddrugresponse AT kenmaes theepigenomeinmultiplemyelomaimpactontumorcellplasticityanddrugresponse AT kimdeveirman theepigenomeinmultiplemyelomaimpactontumorcellplasticityanddrugresponse AT elinemenu theepigenomeinmultiplemyelomaimpactontumorcellplasticityanddrugresponse AT karinvanderkerken theepigenomeinmultiplemyelomaimpactontumorcellplasticityanddrugresponse AT elkedebruyne theepigenomeinmultiplemyelomaimpactontumorcellplasticityanddrugresponse AT evadesmedt epigenomeinmultiplemyelomaimpactontumorcellplasticityanddrugresponse AT huilui epigenomeinmultiplemyelomaimpactontumorcellplasticityanddrugresponse AT huilui epigenomeinmultiplemyelomaimpactontumorcellplasticityanddrugresponse AT kenmaes epigenomeinmultiplemyelomaimpactontumorcellplasticityanddrugresponse AT kimdeveirman epigenomeinmultiplemyelomaimpactontumorcellplasticityanddrugresponse AT elinemenu epigenomeinmultiplemyelomaimpactontumorcellplasticityanddrugresponse AT karinvanderkerken epigenomeinmultiplemyelomaimpactontumorcellplasticityanddrugresponse AT elkedebruyne epigenomeinmultiplemyelomaimpactontumorcellplasticityanddrugresponse |
_version_ |
1716819708081078272 |