ArticleClinical epigenetics2018
PRC2 targeting is a therapeutic strategy for EZ score defined high-risk multiple myeloma patients and overcome resistance to IMiDs.
Article in Clinical epigenetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 46 citations in OpenAlex.
- Inhibition of SUV39H1 as a potent therapeutic target in multiple myeloma.Haematologica · 2026Article
- CD200 immune checkpoint expression is associated with inferior outcome in multiple myeloma patients treated with anti-CD38 monoclonal antibodies.Oncoimmunology · 2025Article
- Multiple myeloma associated long non-coding RNA PLUM confers chemoresistance by enhancing PRC2 mediated UPR pathway activation.Nature communications · 2025Article
- Combinatorial DNMTs and EZH2 inhibition reprograms the H3K27me3 and DNAme-mediated onco-epigenome to suppress multiple myeloma proliferation.Scientific reports · 2025Article
- Targeting transcription-replication conflicts using G-quadruplexes stabilizers in multiple myeloma.Blood neoplasia · 2025Article
- Creation of an innovative diagnostic framework for hepatocellular carcinoma employing bioinformatics techniques focused on senescence-related and pyroptosis-related genes.Frontiers in oncology · 2025Article
- Ironomycin induces mantle cell lymphoma cell death by targeting iron metabolism addiction.Theranostics · 2025Article
- Study on the Effect of EZH2 Inhibitor Combined with TIGIT Monoclonal Antibody against Multiple Myeloma Cells.International journal of molecular sciences · 2023Article
- LAIR1, an ITIM-Containing Receptor Involved in Immune Disorders and in Hematological Neoplasms.International journal of molecular sciences · 2022Review
- The NADPH oxidase NOX2 is a marker of adverse prognosis involved in chemoresistance of acute myeloid leukemias.Haematologica · 2022Article
- Targeting Cellular Iron Homeostasis with Ironomycin in Diffuse Large B-cell Lymphoma.Cancer research · 2022Article
- Pyrroline-5-Carboxylate Reductase 1: a novel target for sensitizing multiple myeloma cells to bortezomib by inhibition of PRAS40-mediated protein synthesis.Journal of experimental & clinical cancer research : CR · 2022Article
- Drug resistance in multiple myeloma: Soldiers and weapons in the bone marrow niche.Frontiers in oncology · 2022Review
- Article
- The BLM helicase is a new therapeutic target in multiple myeloma involved in replication stress survival and drug resistance.Frontiers in immunology · 2022Article
- Insights into high-risk multiple myeloma from an analysis of the role of PHF19 in cancer.Journal of experimental & clinical cancer research : CR · 2021Review
- Ferroptosis Induction in Multiple Myeloma Cells Triggers DNA Methylation and Histone Modification Changes Associated with Cellular Senescence.International journal of molecular sciences · 2021Article
- One Omics Approach Does Not Rule Them All: The Metabolome and the Epigenome Join Forces in Haematological Malignancies.Epigenomes · 2021Review
- RNA-Sequencing-Based Transcriptomic Score with Prognostic and Theranostic Values in Multiple Myeloma.Journal of personalized medicine · 2021Article
- Targeting the methyltransferase SETD8 impairs tumor cell survival and overcomes drug resistance independently of p53 status in multiple myeloma.Clinical epigenetics · 2021Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMultiple myeloma (MM) is a malignant plasma cell disease with a poor survival, characterized by the accumulation of myeloma cells (MMCs) within the bone marrow. Epigenetic modifications in MM are associated not only with cancer development and progression, but also with drug resistance.
methodsWe identified a significant upregulation of the polycomb repressive complex 2 (PRC2) core genes in MM cells in association with proliferation. We used EPZ-6438, a specific small molecule inhibitor of EZH2 methyltransferase activity, to evaluate its effects on MM cells phenotype and gene expression prolile.
resultsPRC2 targeting results in growth inhibition due to cell cycle arrest and apoptosis together with polycomb, DNA methylation, TP53, and RB1 target genes induction. Resistance to EZH2 inhibitor is mediated by DNA methylation of PRC2 target genes. We also demonstrate a synergistic effect of EPZ-6438 and lenalidomide, a conventional drug used for MM treatment, activating B cell transcription factors and tumor suppressor gene expression in concert with MYC repression. We establish a gene expression-based EZ score allowing to identify poor prognosis patients that could benefit from EZH2 inhibitor treatment.
conclusionsThese data suggest that PRC2 targeting in association with IMiDs could have a therapeutic interest in MM patients characterized by high EZ score values, reactivating B cell transcription factors, and tumor suppressor genes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.