Timeline of gene discovery efforts in patients with MPNs. The MPNs were initially grouped together based on prescient clinical insights by William Dameshek in 1951.54 The earliest insights into the genetic causes for the MPNs were then made in 1976 to 1981, when a series of studies by Philip Fialkow et al demonstrated that all 3 classic MPNs represented clonal disorders derived from a genetically aberrant HSC.55-57 This was followed by the discovery of activating mutations in JAK2 and the thrombopoietin receptor MPL in the majority of patients with PV, ET, and PMF in 2005 to 2007. More recently, a series of mutations in genes with the primary known function of epigenetic regulation of transcription have been identified in MPN patients. This includes mutations in TET2, ASXL1, EZH2, and DNMT3A in MPN patients. Finally mutations in the spliceosomal proteins of unclear function have also been found to occur in MPN patients.
