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

• Published in: British journal of haematology 2024-05, Vol.204 (5), p.1838-1843
• Main Authors: Noguera-Castells, Aleix, Campillo-Marcos, Ignacio, Davalos, Veronica, García-Prieto, Carlos A, Valcárcel, David, Molero, Antonieta, Palomo, Laura, Gattermann, Norbert, Wulfert, Michael, Chaparro-González, Lorea, Solé, Francesc, Cabezón, Marta, Jiménez-Lorenzo, María J, Xicoy, Blanca, Zamora, Lurdes, De Stefano, Alessia, Casalin, Irene, Finelli, Carlo, Follo, Matilde Y, Esteller, Manel
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Antimetabolites, Antineoplastic - pharmacology; Antimetabolites, Antineoplastic - therapeutic use; Azacitidine - pharmacology; Azacitidine - therapeutic use; DNA fingerprinting; DNA Methylation; Epigenesis, Genetic - drug effects; Epigenetics; Female; Humans; Male; Middle Aged; Myelodysplastic syndrome; Myelodysplastic Syndromes - drug therapy; Myelodysplastic Syndromes - genetics; Patients; Retrospective Studies; Treatment Outcome
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/bjh.19392

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.