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

Journal of Experimental & Clinical Cancer Research

Michael Bauer¹  Brian A. Walker²  Jinyoung Choi³  Yubao Wang³  Louis Williams³  Eileen M. Boyle³  Hussein Ghamlouch³  Benedetto Bruno³  Faith E. Davies³  Gareth J. Morgan³  Patrick Blaney⁴  Daniel Auclair⁵ 

[1] Department of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, AR, USA;Division of Hematology Oncology, Indiana University, Indianapolis, IN, USA;Myeloma Research Program, NYU Langone Medical Center, Perlmutter Cancer Center, 522 1st Avenue, Manhattan, 10016, New York City, NY, USA;Myeloma Research Program, NYU Langone Medical Center, Perlmutter Cancer Center, 522 1st Avenue, Manhattan, 10016, New York City, NY, USA;Applied Bioinformatics Laboratories (ABL), NYU Langone Medical Center, New York, NY, USA;The Multiple Myeloma Research Foundation (MMRF), Norwalk, CT, USA;

关键词: Multiple Myeloma;    PHF19;    Polycomb Repressive Complex 2;    PRC2;    EZH2;    Epigenetic;    Cancer progression;   

DOI  :  10.1186/s13046-021-02185-1

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY