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- W2894700082 abstract "Multiple 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. We 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. PRC2 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. These 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." @default.
- W2894700082 created "2018-10-12" @default.
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- W2894700082 date "2018-10-03" @default.
- W2894700082 modified "2023-10-09" @default.
- W2894700082 title "PRC2 targeting is a therapeutic strategy for EZ score defined high-risk multiple myeloma patients and overcome resistance to IMiDs" @default.
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- W2894700082 cites W1975024491 @default.
- W2894700082 cites W2010457001 @default.
- W2894700082 cites W2011246614 @default.
- W2894700082 cites W2011924190 @default.
- W2894700082 cites W2017958579 @default.
- W2894700082 cites W2018822911 @default.
- W2894700082 cites W2021028337 @default.
- W2894700082 cites W2023560584 @default.
- W2894700082 cites W2024873523 @default.
- W2894700082 cites W2044169243 @default.
- W2894700082 cites W2049641805 @default.
- W2894700082 cites W2053421436 @default.
- W2894700082 cites W2054414479 @default.
- W2894700082 cites W2057654378 @default.
- W2894700082 cites W2059581635 @default.
- W2894700082 cites W2060916625 @default.
- W2894700082 cites W2060929578 @default.
- W2894700082 cites W2064347825 @default.
- W2894700082 cites W2068447264 @default.
- W2894700082 cites W2075520012 @default.
- W2894700082 cites W2079278201 @default.
- W2894700082 cites W2090022532 @default.
- W2894700082 cites W2091912608 @default.
- W2894700082 cites W2096087418 @default.
- W2894700082 cites W2096642700 @default.
- W2894700082 cites W2101870168 @default.
- W2894700082 cites W2104195581 @default.
- W2894700082 cites W2108495564 @default.
- W2894700082 cites W2108676874 @default.
- W2894700082 cites W2113771680 @default.
- W2894700082 cites W2114396320 @default.
- W2894700082 cites W2115764086 @default.
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- W2894700082 cites W2125477622 @default.
- W2894700082 cites W2130410032 @default.
- W2894700082 cites W2131478115 @default.
- W2894700082 cites W2132725936 @default.
- W2894700082 cites W2146634687 @default.
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- W2894700082 cites W2153252925 @default.
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- W2894700082 cites W2161160225 @default.
- W2894700082 cites W2169456326 @default.
- W2894700082 cites W2171504422 @default.
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- W2894700082 cites W2179438025 @default.
- W2894700082 cites W2186490019 @default.
- W2894700082 cites W2218599835 @default.
- W2894700082 cites W2235371662 @default.
- W2894700082 cites W2261876703 @default.
- W2894700082 cites W2312957112 @default.
- W2894700082 cites W2382652632 @default.
- W2894700082 cites W2414896371 @default.
- W2894700082 cites W2421310884 @default.
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- W2894700082 doi "https://doi.org/10.1186/s13148-018-0554-4" @default.
- W2894700082 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6171329" @default.
- W2894700082 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30285865" @default.
- W2894700082 hasPublicationYear "2018" @default.
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