Diagenode

A distinct metabolic response characterizes sensitivity to EZH2inhibition in multiple myeloma.


Nylund P. et al.

Multiple myeloma (MM) is a heterogeneous haematological disease that remains clinically challenging. Increased activity of the epigenetic silencer EZH2 is a common feature in patients with poor prognosis. Previous findings have demonstrated that metabolic profiles can be sensitive markers for response to treatment in cancer. While EZH2 inhibition (EZH2i) has proven efficient in inducing cell death in a number of human MM cell lines, we hereby identified a subset of cell lines that despite a global loss of H3K27me3, remains viable after EZH2i. By coupling liquid chromatography-mass spectrometry with gene and miRNA expression profiling, we found that sensitivity to EZH2i correlated with distinct metabolic signatures resulting from a dysregulation of genes involved in methionine cycling. Specifically, EZH2i resulted in a miRNA-mediated downregulation of methionine cycling-associated genes in responsive cells. This induced metabolite accumulation and DNA damage, leading to G2 arrest and apoptosis. Altogether, we unveiled that sensitivity to EZH2i in human MM cell lines is associated with a specific metabolic and gene expression profile post-treatment.

Tags
iDeal ChIP-seq Kit for Histones

Share this article

Published
February, 2021

Source

Products used in this publication

  • ChIP kit icon
    C01010051
    iDeal ChIP-seq kit for Histones
  • Bioruptor Pico
    B01080010
    Bioruptor® Pico sonication device

Events

  • Virtual ChIP workshop - January 18-19, 2022 or January 25-26, 2022
    Diagenode
    Jan 18-Jan 26, 2022
  • Virtual DNA Methylation - January 18-19, 2022 or January 25-26, 2022
    Diagenode
    Jan 18-Jan 26, 2022
  • Lausanne Genomics Days 2022
    Lausanne, Switzerland
    Feb 14-Feb 15, 2022
 See all events

News

 See all news


The European Regional Development Fund and Wallonia are investing in your future.

Extension of industrial buildings and new laboratories.


       Site map   |   Contact us   |   Conditions of sales   |   Conditions of purchase   |   Privacy policy   |   Diagenode Diagnostics