title: Mutations profile of polycythemia vera and essential thrombocythemia among Japanese children.
abstract: BACKGROUND
  Acquired somatic mutations of JAK2 have been reported to play a pivotal role in the pathogenesis of BCR-ABL1-negative myeloproliferative neoplasm (MPN). However, the molecular characteristics of childhood MPN remain to be elucidated.
  
  
  METHODS
  We investigated a group of pediatric patients diagnosed either with essential thrombocythemia (ET; N = 9) or polycythemia vera (PV; N = 4) according to WHO criteria (median age = 10 years; range 1.5-15 years) in whom direct sequencing was performed for the existence of genetic alterations in JAK2, MPL, TET2, ASXL1, CBL, IDH1, and IDH2. More sensitive allele specific polymerase chain reaction was used for JAK2(V617F) genotyping.
  
  
  RESULTS
  We found three patients harbor JAK2(V617F) mutation (2/9 ET and 1/4 PV). Bone marrow examination showed small and large megakaryocytes with dysplastic features in JAK2(V617F)-positive ET patients compared to those without JAK2(V617F). We identified a previously unrecognized missense mutation at codon 1230 in exon 12 of ASXL1 gene in ET and PV patients (1/9 ET and 1/4 PV). Otherwise, no genetic alterations could be detected in JAK2 exon 12, MPL, TET2, CBL, IDH1, and IDH2 in all ET and PV patients.
  
  
  CONCLUSIONS
  Although JAK2 mutations in childhood ET and PV are not as frequent as reported in adult patients, JAK2 is the most frequently mutated gene in childhood MPN known so far. Owing to the presence of childhood MPN without any genetic alterations in JAK2, MPL, TET2, ASXL1, CBL, IDH1, and IDH2, new biological markers have to be found.
authors: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors: Olfat
authors: O
authors: Ismael
authors: Akira
authors: A
authors: Shimada
authors: Asahito
authors: A
authors: Hama
authors: Hiroshi
authors: H
authors: Sakaguchi
authors: Sayoko
authors: S
authors: Doisaki
authors: Hideki
authors: H
authors: Muramatsu
authors: Nao
authors: N
authors: Yoshida
authors: Masafumi
authors: M
authors: Ito
authors: Yoshiyuki
authors: Y
authors: Takahashi
authors: Naohiro
authors: N
authors: Akita
authors: Shosuke
authors: S
authors: Sunami
authors: Yoshitoshi
authors: Y
authors: Ohtsuka
authors: Youji
authors: Y
authors: Asada
authors: Hiroyuki
authors: H
authors: Fujisaki
authors: Seiji
authors: S
authors: Kojima
mesh_terms: D000293:Adolescent; D044466:Asian People; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D009154:Mutation; D011087:Polycythemia Vera / Q000235:genetics*; D013920:Thrombocythemia, Essential / Q000235:genetics*
chemical_list: C507924:JAK2 protein, human; D053614:Janus Kinase 2