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 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.

EZH2 Promotes Multiple Myeloma Progression via STAT3 Pathway Activation

“…Previous researches have reported the overexpression of EZH2 without mutation in MM [22][23][24]. Additionally, despite the heterogeneity observed in MM, bone marrow cells isolated from patients with MM or MM cell lines displayed constitutive activation and up-regulation of STAT3, while no mutations were observed [25,26].…”

Effects of methane emissions on multiple myeloma-related mortality rates: A World Health Organization perspective

“…Multiple myeloma is a type of cancer consisting of white blood cells called plasma cells, [16][17][18] and plasma cells increase uncontrollably, as in other types of cancer. [19][20][21][22][23] Although there have been serious advances in the field of health and especially in the cancer diagnosis and treatment process, deaths due to MM are still considered an important public health problem. [19][20][21][22][23] Although there are many risk factors in deaths caused by MM, the number of studies focusing on environmental factors is quite limited.…”

“…[19][20][21][22][23] Although there have been serious advances in the field of health and especially in the cancer diagnosis and treatment process, deaths due to MM are still considered an important public health problem. [19][20][21][22][23] Although there are many risk factors in deaths caused by MM, the number of studies focusing on environmental factors is quite limited. Methane emission is a subject studied in areas such as global warming, [24,25] especially the marine environment and ocean fauna.…”

Deciphering the dual roles of PHD finger proteins from oncogenic drivers to tumor suppressors

“…This catalysis of histone mark H3K27me3 affects the expression of crucial genes that govern cell proliferation and differentiation, thereby facilitating cancer progression by altering gene expression patterns and promoting genetic instability within MM cells. Understanding PHF19’s dual role in chromatin remodeling and gene expression provides new avenues for targeted therapies in aggressive MM subsets ( Ghamlouch et al, 2021 ).…”