title: Clinical correlates of the presence of the Asp816Val c-kit mutation in the peripheral blood mononuclear cells of patients with mastocytosis.
abstract: BACKGROUND
  The Asp816Val mutation in the catalytic domain of the c-kit receptor has been identified in patients with systemic mastocytosis.
  
  
  METHODS
  To determine whether this mutation is associated with identifiable clinical patterns of disease and prognosis, a total of 65 patients with mastocytosis were screened for the presence of the Asp816Val mutation in peripheral blood mononuclear cells (PBMCs).
  
  
  RESULTS
  By analysis of HinfI digestion products, the authors found that the overall prevalence of this mutation in the current patient series was 25%. The presence of the Asp816Val mutation in PBMCs was observed in 15 adults (of 16 Asp816Val mutation positive patients) and 1 infant, but not in any children with mastocytosis. Patients whose PBMCs were positive for this mutation (category II and a subset of category Ib mastocytosis patients) manifested a more severe disease pattern, with clinical features ranging in severity from early to advanced myelodysplastic or myeloproliferative syndromes. These patients more commonly had osteosclerotic bone involvement (a clinical feature primarily observed in mastocytosis patients with an associated hematologic disorder) as well as immunoglobulin dysregulation and peripheral blood abnormalities. Furthermore, pedigree analysis of three families provided evidence that the mutation was somatic.
  
  
  CONCLUSIONS
  Twenty-five percent of all patients with mastocytosis had the Asp816Val mutation in PBMCs; 56% of these patients had evidence of a myelodysplastic or myeloproliferative syndrome, and 44% had been clinically placed in the indolent mastocytosis category, suggesting that the current classification scheme used to assign prognosis may be inadequate. Therefore, determination of the presence or absence of this mutation in PBMCs of mastocytosis patients offers a useful adjunct in determining the extent of workup and assigning prognosis in this complex and heterogeneous disease.
authors.affiliation: Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-1881, USA.
authors.forename: A S
authors.initials: AS
authors.lastname: Worobec
authors.forename: T
authors.initials: T
authors.lastname: Semere
authors.forename: H
authors.initials: H
authors.lastname: Nagata
authors.forename: D D
authors.initials: DD
authors.lastname: Metcalfe
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001847:Bone Diseases / Q000000981:diagnostic imaging; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007963:Leukocytes, Mononuclear / Q000737:chemistry*; D008297:Male; D008415:Mastocytosis / Q000097:blood / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D017354:Point Mutation; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D011859:Radiography
chemical_list: D019009:Proto-Oncogene Proteins c-kit