title: The epigenomics revolution in myelodysplasia: a clinico-pathological perspective.
abstract: Rapid advances in molecular technologies are continually re-shaping the way we view and understand the mechanisms driving oncogenesis. The last decade has witnessed unparalleled change in the biology and therapy of the myelodysplastic syndromes (MDS), a heterogeneous collection of clonal myeloid disorders characterised by ineffective haematopoiesis and susceptibility to acute leukaemia transformation. Pivotal studies demonstrating the positive effects of hypomethylating agents on clinical outcome have brought an 'epigenomics revolution' to this disease, emphasising the importance of epigenetic mechanisms to the underlying pathogenesis of MDS. One of the most important future challenges in the MDS field will be to determine whether epigenetic therapies can be made more 'targeted' through identification of biomarkers which define subsets of patients most likely to benefit from treatment. A wave of novel mutations have recently been reported in MDS and other myeloid disorders, several of which regulate endogenous methylation networks within cells (including TET2, DNMT3A, IDH and EZH2). The relevance of these lesions in being able to predict response to epigenetic modulators and their correlation with epigenetic signatures in MDS are beginning to emerge.
authors: Department of Clinical Haematology, The Alfred Hospital, Monash University, Melbourne, Victoria, Australia.
authors: Peter T
authors: PT
authors: Tan
authors: Andrew H
authors: AH
authors: Wei
mesh_terms: D019175:DNA Methylation / Q000187:drug effects; D004273:DNA, Neoplasm / Q000032:analysis; D057890:Epigenomics; D006801:Humans; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm