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Multi-omics analysis of myelodysplastic syndromes resistance to epigenetics threrary reveals PI3K/Akt activation mediated by epigenetic silencing of PTEN and epi-transcriptional silencing of MDM2 [epitranscriptome]

ABSTRACT: Myelodysplastic syndrome (MDS) is a clonal myeloid neoplasm characterized by ineffective haematopoiesis and cytopenia with frequent epigenetic modifications. Hypomethylating agents (HMA) such as azacitidine (AZA) and decitabine (DEC) are standard therapeutic options in MDS, but drug resistance is not uncommon.To study RNA modification in particular M6A, P39-AZA-S and P39-AZA-R native RNA libraries were prepared using the direct RNA sequencing kit (Oxford Nanopore) following the manufacturer’s protocol (SQK-RNA002). Differential methylated RNA signal called from raw fast5 files were used as input for basecalling and downstream mapping and methylated transcript detection.

ORGANISM(S): Homo sapiens

PROVIDER: GSE165064 | GEO | 2022/06/01

REPOSITORIES: GEO

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Multi-omics analysis of myelodysplastic syndromes resistance to epigenetics threrary reveals PI3K/Akt activation mediated by epigenetic silencing of PTEN and epi-transcriptional silencing of MDM2 [transcriptome]

Project description:Myelodysplastic syndrome (MDS) is a clonal myeloid neoplasm characterized by ineffective haematopoiesis and cytopenia with frequent epigenetic modifications. Hypomethylating agents (HMA) such as azacitidine (AZA) and decitabine (DEC) are standard therapeutic options in MDS, but drug resistance is not uncommon. Herein, multi-omic analysis is used to identify signaling pathways during MDS HMA resistance using MDS cell line P39 and validated in P39 and Kasumi-1. The Illumina Infinium Methylation EPIC BeadChip (850k) was used for comparison of P39-AZA-S and P39-DEC-S (control group) and P39-AZA-R and P39-DEC-R (resistant group). Sampple was prepared following the manufacturer protocol and final chip imaging was performed on Illumina iScan System (Illumina). Bioinformatic analysis of Methylation EPIC data utilized the Illumina GenomeStudio Methylation module V2011. Only CpG sites passed quality controls were filtered and normalized for differential methylation calculation.

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