Insights into high-risk multiple myeloma from an analysis of the role of PHF19 in cancer

Abstract Despite improvements in outcome, 15-25% of newly diagnosed multiple myeloma (MM) patients have treatment resistant high-risk (HR) disease with a poor survival. The lack of a genetic basis for HR has focused attention on the role played by epigenetic changes. Aberrant expression and somatic...

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Autores principales:	Hussein Ghamlouch, Eileen M. Boyle, Patrick Blaney, Yubao Wang, Jinyoung Choi, Louis Williams, Michael Bauer, Daniel Auclair, Benedetto Bruno, Brian A. Walker, Faith E. Davies, Gareth J. Morgan
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Multiple Myeloma PHF19 Polycomb Repressive Complex 2 PRC2 EZH2 Epigenetic Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/461e41ddf12c4094a177bd08ae6ef5ec
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spelling	oai:doaj.org-article:461e41ddf12c4094a177bd08ae6ef5ec2021-12-05T12:10:11ZInsights into high-risk multiple myeloma from an analysis of the role of PHF19 in cancer10.1186/s13046-021-02185-11756-9966https://doaj.org/article/461e41ddf12c4094a177bd08ae6ef5ec2021-12-01T00:00:00Zhttps://doi.org/10.1186/s13046-021-02185-1https://doaj.org/toc/1756-9966Abstract Despite improvements in outcome, 15-25% of newly diagnosed multiple myeloma (MM) patients have treatment resistant high-risk (HR) disease with a poor survival. The lack of a genetic basis for HR has focused attention on the role played by epigenetic changes. Aberrant expression and somatic mutations affecting genes involved in the regulation of tri-methylation of the lysine (K) 27 on histone 3 H3 (H3K27me3) are common in cancer. H3K27me3 is catalyzed by EZH2, the catalytic subunit of the Polycomb Repressive Complex 2 (PRC2). The deregulation of H3K27me3 has been shown to be involved in oncogenic transformation and tumor progression in a variety of hematological malignancies including MM. Recently we have shown that aberrant overexpression of the PRC2 subunit PHD Finger Protein 19 (PHF19) is the most significant overall contributor to HR status further focusing attention on the role played by epigenetic change in MM. By modulating both the PRC2/EZH2 catalytic activity and recruitment, PHF19 regulates the expression of key genes involved in cell growth and differentiation. Here we review the expression, regulation and function of PHF19 both in normal and the pathological contexts of solid cancers and MM. We present evidence that strongly implicates PHF19 in the regulation of genes important in cell cycle and the genetic stability of MM cells making it highly relevant to HR MM behavior. A detailed understanding of the normal and pathological functions of PHF19 will allow us to design therapeutic strategies able to target aggressive subsets of MM.Hussein GhamlouchEileen M. BoylePatrick BlaneyYubao WangJinyoung ChoiLouis WilliamsMichael BauerDaniel AuclairBenedetto BrunoBrian A. WalkerFaith E. DaviesGareth J. MorganBMCarticleMultiple MyelomaPHF19Polycomb Repressive Complex 2PRC2EZH2EpigeneticNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENJournal of Experimental & Clinical Cancer Research, Vol 40, Iss 1, Pp 1-23 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Multiple Myeloma PHF19 Polycomb Repressive Complex 2 PRC2 EZH2 Epigenetic Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Multiple Myeloma PHF19 Polycomb Repressive Complex 2 PRC2 EZH2 Epigenetic Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Hussein Ghamlouch Eileen M. Boyle Patrick Blaney Yubao Wang Jinyoung Choi Louis Williams Michael Bauer Daniel Auclair Benedetto Bruno Brian A. Walker Faith E. Davies Gareth J. Morgan Insights into high-risk multiple myeloma from an analysis of the role of PHF19 in cancer
description	Abstract Despite improvements in outcome, 15-25% of newly diagnosed multiple myeloma (MM) patients have treatment resistant high-risk (HR) disease with a poor survival. The lack of a genetic basis for HR has focused attention on the role played by epigenetic changes. Aberrant expression and somatic mutations affecting genes involved in the regulation of tri-methylation of the lysine (K) 27 on histone 3 H3 (H3K27me3) are common in cancer. H3K27me3 is catalyzed by EZH2, the catalytic subunit of the Polycomb Repressive Complex 2 (PRC2). The deregulation of H3K27me3 has been shown to be involved in oncogenic transformation and tumor progression in a variety of hematological malignancies including MM. Recently we have shown that aberrant overexpression of the PRC2 subunit PHD Finger Protein 19 (PHF19) is the most significant overall contributor to HR status further focusing attention on the role played by epigenetic change in MM. By modulating both the PRC2/EZH2 catalytic activity and recruitment, PHF19 regulates the expression of key genes involved in cell growth and differentiation. Here we review the expression, regulation and function of PHF19 both in normal and the pathological contexts of solid cancers and MM. We present evidence that strongly implicates PHF19 in the regulation of genes important in cell cycle and the genetic stability of MM cells making it highly relevant to HR MM behavior. A detailed understanding of the normal and pathological functions of PHF19 will allow us to design therapeutic strategies able to target aggressive subsets of MM.
format	article
author	Hussein Ghamlouch Eileen M. Boyle Patrick Blaney Yubao Wang Jinyoung Choi Louis Williams Michael Bauer Daniel Auclair Benedetto Bruno Brian A. Walker Faith E. Davies Gareth J. Morgan
author_facet	Hussein Ghamlouch Eileen M. Boyle Patrick Blaney Yubao Wang Jinyoung Choi Louis Williams Michael Bauer Daniel Auclair Benedetto Bruno Brian A. Walker Faith E. Davies Gareth J. Morgan
author_sort	Hussein Ghamlouch
title	Insights into high-risk multiple myeloma from an analysis of the role of PHF19 in cancer
title_short	Insights into high-risk multiple myeloma from an analysis of the role of PHF19 in cancer
title_full	Insights into high-risk multiple myeloma from an analysis of the role of PHF19 in cancer
title_fullStr	Insights into high-risk multiple myeloma from an analysis of the role of PHF19 in cancer
title_full_unstemmed	Insights into high-risk multiple myeloma from an analysis of the role of PHF19 in cancer
title_sort	insights into high-risk multiple myeloma from an analysis of the role of phf19 in cancer
publisher	BMC
publishDate	2021
url	https://doaj.org/article/461e41ddf12c4094a177bd08ae6ef5ec
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Insights into high-risk multiple myeloma from an analysis of the role of PHF19 in cancer

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