title: Genetics of the myeloproliferative neoplasms.
abstract: OBJECTIVE
  Since the discovery of the JAK2V617F mutation in 2005, an increasing number of somatic and germline genetic events responsible for myeloproliferative neoplasm (MPN) pathogenesis have been uncovered. The purpose of this review is to outline the most recent discoveries of the genetic alterations found in patients with MPNs.
  
  
  RESULTS
  In addition to the JAK2V617F mutation, additional mutations in the JAK–STAT pathway have been discovered including a series of mutations in exon 12 of JAK2, the thrombopoietic receptor gene MPL, and in the gene encoding the JAK–STAT inhibitory adaptor protein LNK. Additionally, mutations in genes which appear to affect the epigenome of MPN patients have been discovered including mutations in TET2, IDH1/ 2, EZH2, and ASXL1. Lastly, some insights into the genetic events which contribute to transformation of a chronic MPN phenotype to acute myeloid leukemia have been elucidated, including deletion of the transcription factor Ikaros.
  
  
  CONCLUSIONS
  The spectrum of genetic abnormalities found in the classic MPNs has increased over the last 6 years and somatic mutations in JAK2, MPL, LNK, TET2, EZH2, ASXL1, and IDH1/2 have all been described. Despite this, the initiating genetic events responsible for the development of MPNs is still not totally understood.
authors.affiliation: Human Oncology and Pathogenesis Program and Leukemia Service, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA. abdelwao@mskcc.org
authors.forename: Omar
authors.initials: O
authors.lastname: Abdel-Wahab
mesh_terms: D004268:DNA-Binding Proteins / Q000235:genetics; D049308:Dioxygenases; D000071221:Enhancer of Zeste Homolog 2 Protein; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D053614:Janus Kinase 2 / Q000235:genetics; D009196:Myeloproliferative Disorders / Q000235:genetics*; D063151:Polycomb Repressive Complex 2; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
chemical_list: C473949:ASXL1 protein, human; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D049308:Dioxygenases; C541081:TET2 protein, human; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2; C507924:JAK2 protein, human; D053614:Janus Kinase 2