title: KIT D816V mutation burden does not correlate to clinical manifestations of indolent systemic mastocytosis.
abstract: BACKGROUND
  Clinical manifestations of indolent systemic mastocytosis (ISM) comprise mediator-related symptoms, anaphylaxis, and osteoporosis. A new sensitive method for KIT D816V mutation detection allows quantification of the level of mutation-positive cells.
  
  
  OBJECTIVE
  To investigate whether the fraction of KIT D816V positive cells in peripheral blood (PB) or bone marrow (BM) aspirate in adult patients with ISM correlates with clinical manifestations of the disease.
  
  
  METHODS
  We included 48 adult patients with ISM (28 females/20 males) from our center in whom the KIT D816V mutation level in both BM aspirate and PB was analyzed. For each patient, the severity of mediator-related symptoms (skin, gastrointestinal, musculoskeletal, and neuropsychiatric) and episodes of anaphylaxis were evaluated by interview and medical record files. Bone mineral density was determined by using dual-energy x-ray absorptiometry.
  
  
  RESULTS
  Median fraction (range) of KIT D816V positive cells was 0.6 (0.01%-90%) in BM and 0.3 (0.003%-49%) in PB. Mutation level did not differ between patients with none/mild symptoms and patients with moderate/severe symptoms, patients with and without anaphylaxis, or patients with osteoporosis/osteopenia and normal bone mineral density. No significant differences in clinical profile were detected in patients with different levels of mutation except for an indication of longer disease duration and age in patients with highest mutation levels.
  
  
  CONCLUSIONS
  To our knowledge, this is the first report on the clinical impact of the fraction of KIT D816V mutation positive cells in ISM, which in the present study does not seem to correlate with clinical manifestations of the disease.
authors.affiliation: Department of Dermatology and Allergy Centre, Odense University Hospital, Odense, Denmark; Institute of Clinical Research, University of Southern Denmark, Odense, Denmark. Electronic address: sigurd.broesby-olsen@ouh.regionsyddanmark.dk.
authors.forename: Sigurd
authors.initials: S
authors.lastname: Broesby-Olsen
authors.affiliation: Department of Pathology, Odense University Hospital, Odense, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kristensen
authors.affiliation: Institute of Clinical Research, University of Southern Denmark, Odense, Denmark; Department of Hematology, Odense University Hospital, Odense, Denmark.
authors.forename: Hanne
authors.initials: H
authors.lastname: Vestergaard
authors.affiliation: Institute of Clinical Research, University of Southern Denmark, Odense, Denmark; Department of Endocrinology, Odense University Hospital, Odense, Denmark.
authors.forename: Kim
authors.initials: K
authors.lastname: Brixen
authors.affiliation: Institute of Clinical Research, University of Southern Denmark, Odense, Denmark; Department of Pathology, Odense University Hospital, Odense, Denmark.
authors.forename: Michael Boe
authors.initials: MB
authors.lastname: Møller
authors.affiliation: Department of Dermatology and Allergy Centre, Odense University Hospital, Odense, Denmark; Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.
authors.forename: Carsten
authors.initials: C
authors.lastname: Bindslev-Jensen
mesh_terms: D000328:Adult; D000368:Aged; D000707:Anaphylaxis / Q000150:complications / Q000235:genetics; D001854:Bone Marrow Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D034721:Mastocytosis, Systemic / Q000150:complications / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D010024:Osteoporosis / Q000150:complications / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D019009:Proto-Oncogene Proteins c-kit
keywords: BM; BMD; Bone marrow; Bone mineral density; DXA; Dual-energy x-ray absorptiometry; GI; Gastrointestinal; ISM; Indolent systemic mastocytosis; KIT D816V; MCs; Mast cells; PB; Peripheral blood; SM; Systemic mastocytosis; allele burden; anaphylaxis; mast cell; mutation burden; osteoporosis