DNA methylation profiling of myelodysplastic syndromes and clinical response to azacitidine : A multicentre retrospective study

DV reports personal fees from BMS/Celgene, Amgen, Astellas, Agios, Grifols, Janssen, MSD, Novartis, Pfizer, Sanofi, Sobi and Takeda outside the submitted work. AM reports personal fees from Oryzon genomics and AstraZeneca; non-financial support from Novartis and Jazz pharmaceuticals outside the submitted work. LZ reports grants and personal fees from Celgene/BMS, Incyte, and Novartis outside the submitted work. CF declares research funding, advisory committees and speaker fees from Celgene BMS, advisory committees and speaker fees from Novartis and consultancy from Takeda. ME declares grants from Ferrer International and Incyte; and personal fees from Quimatryx, outside the submitted work. No disclosures were reported by the other authors. Real-world data have revealed that a substantial portion of patients with myelodysplastic syndromes (MDS) does not respond to epigenetic therapy with hypomethylating agents (HMAs). The cellular and molecular reasons for this resistance to the demethylating agent and biomarkers that would be able to predict the treatment refractoriness are largely unknown. In this study, we shed light on this enigma by characterizing the epigenomic profiles of patients with MDS treated with azacitidine. Our approach provides a comprehensive view of the evolving DNA methylation architecture of the disease and holds great potential for advancing our understanding of MDS treatment responses to HMAs.