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A wide array of recurring genetic mutations involved in <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> splicing, histone manipulation, <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> methylation, transcription factors, kinase signaling, <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> repair, cohesin proteins, and other signal transduction elements has been identified as important substrates for the development of <jats:styled-content style=\"fixed-case\">MDS<\/jats:styled-content>. Cytogenetic abnormalities, namely those characterized by loss of genetic material (including 5q\u2010 and 7q\u2010), have also been strongly implicated and may influence the clonal architecture which predicts such mutations and may provoke an inflammatory bone marrow microenvironment as the substrate for clonal expansion. Other aspects of the molecular pathogenesis of <jats:styled-content style=\"fixed-case\">MDS<\/jats:styled-content> continue to be further elucidated, predicated upon advances in gene expression profiling and the development of new, and improved high\u2010throughput techniques. More accurate understanding of the genetic and molecular basis for the development of <jats:styled-content style=\"fixed-case\">MDS<\/jats:styled-content> directly provides additional opportunity for treatment, which to date remains limited. In this comprehensive review, we examine the current understanding of the molecular pathogenesis and pathophysiology of <jats:styled-content style=\"fixed-case\">MDS<\/jats:styled-content>, as well as review future prospects which may enhance this understanding, treatment strategies, and hopefully outcomes.<\/jats:p>","DOI":"10.1111\/ejh.13092","type":"journal-article","created":{"date-parts":[[2018,5,9]],"date-time":"2018-05-09T19:44:59Z","timestamp":1525895099000},"page":"260-271","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["The genetic and molecular pathogenesis of myelodysplastic syndromes"],"prefix":"10.1111","volume":"101","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8542-2944","authenticated-orcid":false,"given":"Rory M.","family":"Shallis","sequence":"first","affiliation":[{"name":"Division of Hematology\/Medical Oncology Department of Medicine Yale University School of Medicine  New Haven CT 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