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]

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. Resistant cell line of MDS and AML was derived from HMA Azacytidine or Decitabine.