title: Differences in the JAK2 and MPL mutation status in the cell lineages of the bcr/abl-negative chronic myeloproliferative neoplasm subtypes.
abstract: OBJECTIVE
  While the somatic mutation of Janus Kinase 2 (JAK2) and the thrombopoietin receptor (c-MPL) gene are thought to affect the pathogenesis of bcr/abl negative chronic myeloproliferative neoplasm (MPN), the relationship between the mutation and the clinical features remain obscure.
  
  
  METHODS
  The mutation status of these genes in granulocytes, platelets, T-cells, and erythroid colonies (BFU-E) was obtained from 115 MPN patients, and then the clinical features of the MPN subtypes were compared.
  
  
  RESULTS
  The JAK2-V617F mutation was observed in three lineages of granulocytes, platelets, and BFU-E in almost all polycythemia vera (PV) and primary myelofibrosis (PMF) patients. In contrast, 68% of essential thrombocythemia (ET) patients have the JAK2-V617F mutation in at least one of the lineages, of which 70% of these patients have the JAK2-V617F mutation in three lineages; the remaining ET patients with the JAK2-V617F mutation only exhibited the mutation in one or two lineages. Further, the ET patients that exhibited the JAK2-V617F mutation in three lineages had higher WBC and granulocyte counts as compared to the ET patients that did not have the JAK2-V617F mutation or only had the mutation in one or two lineages. Concerning the MPL gene, two ET patients had the MPL-W515L gene mutation in their platelets, although the lineage of the JAK2-V617F mutation involved differed from case to case.
  
  
  CONCLUSIONS
  The progenitor cells that are involved with the JAK2-V617F mutation in MPNs are different in each subtype and this difference may also affect the clinical features of MPNs.
authors: Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, Japan.
authors: Kohtaro
authors: K
authors: Toyama
authors: Masamitsu
authors: M
authors: Karasawa
authors: Akihiko
authors: A
authors: Yokohama
authors: Takeki
authors: T
authors: Mitsui
authors: Hideki
authors: H
authors: Uchiumi
authors: Takayuki
authors: T
authors: Saitoh
authors: Hiroshi
authors: H
authors: Handa
authors: Hirokazu
authors: H
authors: Murakami
authors: Yoshihisa
authors: Y
authors: Nojima
authors: Norifumi
authors: N
authors: Tsukamoto
mesh_terms: D019070:Cell Lineage / Q000235:genetics*; D002478:Cells, Cultured; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D009196:Myeloproliferative Disorders / Q000235:genetics* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000473:pathology; D016315:Proto-Oncogene Proteins c-abl / Q000235:genetics*; D051562:Proto-Oncogene Proteins c-bcr / Q000235:genetics*; D053628:Receptors, Thrombopoietin / Q000235:genetics*
chemical_list: D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D016315:Proto-Oncogene Proteins c-abl; C496613:BCR protein, human; D051562:Proto-Oncogene Proteins c-bcr