Raajit Rampal, MD, PhD, Memorial Sloan-Kettering Cancer Center, New York, NY, discusses the association between methylation profile and response to decitabine-based therapy for patients with accelerated (AP) and blast phase (BP) myeloproliferative neoplasms (MPNs). Analysis of samples available from the MPD-RC 109 study (NCT02076191), which tested the safety and efficacy of ruxolitinib in combination with decitabine, demonstrated that the methylation profile of MPN-AP/BP may predict response to hypomethylating agent-based therapies, such as decitabine. IDH2-mutant MPN-AP/BP was found to be epigenetically distinct. Further validation of these observations is required. This interview took place during the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, 2020.