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Series GSE109674 Query DataSets for GSE109674
Status Public on Jan 25, 2019
Title Dual inhibition of EZH1/2 depletes stem cells and over-activates WNT signaling in multiple myeloma [ChIP-seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Multiple myeloma (MM) is a hematological malignancy caused by accumulation of abnormal clonal plasma cells. Despite the recent development of novel therapies, relapse of MM eventually occurs due to a remaining population of drug-resistant myeloma stem cells. Side population (SP) cells exhibit cancer stem cell-like characteristics in MM; thus targeting these cells is a promising strategy to completely cure this malignancy. Here, we showed that SP cells expressed higher levels of enhancer of zeste (EZH) 1 and EZH2, which encode the catalytic subunits of Polycomb repressive complex 2 (PRC2), than non-SP cells, suggesting that EZH1/2 are both potential therapeutic targets to eradicate myeloma stem cells. A novel EZH1/2 dual inhibitor, OR-S1, effectively eradicated SP cells and had a greater antitumor effect than a selective EZH2 inhibitor in vitro and in vivo, including in a patient-derived xenograft model. Moreover, long-term continuous administration of OR-S1 completely cured mice bearing orthotopic xenografts. Additionally, PRC2 directly regulated WNT signaling, and over-activation of this signaling induced by dual inhibition of EZH1/2 eradicated myeloma stem cells. Our results demonstrate that dual inhibition of EZH1/2 is a promising therapeutic approach to eradicate myeloma stem cells, leading to significant advances in the treatment of MM.
 
Overall design Histone modifications of two MM cell lines were examined by deep sequencing.
 
Contributor(s) Nakagawa M, Kitabayashi I
Citation(s) 30343511
Submission date Jan 25, 2018
Last update date Apr 26, 2019
Contact name Makoto Nakagawa
E-mail(s) maknakag@ncc.go.jp
Organization name National Cancer Center Research Institute
Department Division of Hematological Malignancy
Street address 5-1-1, Tsukiji, Chuo-ku
City Tokyo
ZIP/Postal code 104-0045
Country Japan
 
Platforms (1)
GPL15520 Illumina MiSeq (Homo sapiens)
Samples (4)
GSM2948309 MM.1S_H3K27me3
GSM2948310 MM.1S_input
GSM2948311 RPMI8226_H3K27me3
This SubSeries is part of SuperSeries:
GSE109675 Dual inhibition of EZH1/2 depletes stem cells and over-activates WNT signaling in multiple myeloma
Relations
BioProject PRJNA431631
SRA SRP131407

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Supplementary file Size Download File type/resource
GSE109674_RAW.tar 445.7 Mb (http)(custom) TAR (of BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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