Herviou L, Kassambara A, Boireau S, Robert N, Requirand G, Müller-Tidow C, Vincent L, Seckinger A, Goldschmidt H, Cartron G, Hose D, Cavalli G, Moreaux J. PRC2 targeting is a therapeutic strategy for EZ score defined high-risk multiple myeloma patients and overcome resistance to IMiDs. Clinical Epigenetics. 2018. Download the PDF
Summary of the Study
Epigenetic modifications contribute to multiple myeloma (MM) pathogenesis and drug resistance. This study focuses on targeting the polycomb repressive complex 2 (PRC2) using an EZH2 inhibitor and proposes a risk stratification tool to identify responsive patients.
Key findings
PRC2 genes are upregulated in proliferative MM cells
Treatment with EPZ-6438 (EZH2 inhibitor) leads to:
- Cell cycle arrest and apoptosis
- Upregulation of tumor suppressors and B cell transcription factors
- Repression of MYC
Resistance to EZH2i is linked to DNA methylation of PRC2 targets
Combination with lenalidomide (IMiD) yields synergistic effects
Developed and validated the EZ score, a gene expression–based prognostic tool identifying high-risk patients benefiting from PRC2 inhibition
In this study, Alboukadel Kassambara contributed to the data analysis, specifically in the development and validation of the EZ score, a gene expression–based risk stratifier predicting benefit from EZH2-targeted therapy in high-risk myeloma patients.
Citation
Publication: In Clinical Epigenetics
Date: October 3, 2018
Type: Journal Article
PDF: Download the PDF
Scientific Contributions
Here are more scientific abstracts authored or co-authored by Alboukadel Kassambara. These contributions span computational biology, bioinformatics, biostatistics, machine learning, and multi-omics, with a focus on immuno-oncology and translational research.
