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Series GSE148314 Query DataSets for GSE148314
Status Public on Apr 09, 2020
Title A new hypomethylating agent, OR-2100, resists degradation by cytidine deaminase, leading to favorable oral absorbability and anti-leukemia effects
Organism Homo sapiens
Experiment type Methylation profiling by genome tiling array
Summary DNA methyltransferase inhibitors have improved the prognosis of myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML). However, these agents must be administered intravenously or subcutaneously because they are degraded easily by cytidine deaminase (CDA). OR2100 (OR21), an oligonucleotide comprising decitabine nucleoside 5'-O-trisilylate, resists degradation by CDA. Direct duodenal administration led to high plasma concentrations of OR21 in a cynomolgus monkey model. Transcriptome and methylome analysis of MDS and AML cell lines revealed that OR21 enriched expression of genes associated with tumour suppression, cell differentiation, and immune system processes via alteration of regional promoter methylation. Conversely, immune system process pathways were downregulated in azacytidine-resistant AML cells, indicating that these pathways play a pivotal role in the action of hypomethylating agents. Both in vivo and in vitro, OR21 showed anti-leukaemia effects against MDS and AML cells (including AZA-resistant), and a better safety profile than decitabine. These results suggest that OR21 is a candidate drug for a phase 1 study as an alternative to DAC.
 
Overall design To investigate the effect of OR2100, comparing the gene expressions between OR2100 treated cells and untreated cells.
 
Contributor(s) Ureshino H, Kurahashi Y, Watanabe T, Yamashita S, Kamachi K, Fukuda-Kurahashi Y, Yoshida N, Hattori N, Hayashi Y, Tohyama K, Okada S, Harada H, Ushijima T, Kimura S
Citation(s) 34045225
Submission date Apr 08, 2020
Last update date Jan 13, 2023
Contact name Shinya Kimura
E-mail(s) shkimu@cc.saga-u.ac.jp
Phone +81952342366
Organization name Saga University
Department Drug Discovery and Biomedical Sciences, Faculty of Medicine
Street address 5-1-1 Nabeshima
City Saga
ZIP/Postal code 849-8501
Country Japan
 
Platforms (1)
GPL21145 Infinium MethylationEPIC
Samples (15)
GSM4460148 HL60 Parent control
GSM4460149 HL60 Parent AZA treated
GSM4460150 HL60 Parent OR21 treated
Relations
BioProject PRJNA623877

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE148314_OR21forMDS_normalized_data.txt.gz 69.6 Mb (ftp)(http) TXT
GSE148314_RAW.tar 161.2 Mb (http)(custom) TAR
GSE148314_non-normalized_data.txt.gz 174.0 Mb (ftp)(http) TXT
Processed data are available on Series record

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