Novartis Found Symp. 2005:271:232-42; discussion 242-9.


Systemic mast cell disorders in most instances appear to be clonal disorders of the mast cell and its progenitor. Symptoms result from a pathological release of mast cell mediators and a destructive mast cell infiltration. Cutaneous mastocytosis is most frequently seen in children and may regress. Systemic mastocytosis (SM) is a persistent disease. A somatic c-kit mutation at codon 816 is often detectable in haematopoietic cells. The clinical course of mastocytosis is variable, ranging from indolent to aggressive. Five categories of disease are recognized: Indolent SM, aggressive SM, SM with associated clonal haematological non-mast cell-lineage disease (AHNMD) and mast cell leukaemia (MCL). In SM-AHNMD, additional genetic abnormalities have been reported. Patients with cutaneous or indolent systemic disease are treated symptomatically. Patients with aggressive disease are candidates for cytoreductive therapy. The use of 'Kit-targeting' tyrosine kinase inhibitors are best selected following a mutational analysis of c-kit. For instance, the D816V mutation appears to be associated with relative resistance against imatinib. However, imatinib has been used with success in patients with SM-hypereosinophilic syndrome (HES) and the FIPL1/PDGFRA fusion gene and in a patient with mastocytosis with a mutation outside of codon 816. The value of bone marrow transplantation remains under investigation.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Mast Cells / immunology*
  • Mastocytosis* / classification
  • Mastocytosis* / diagnosis
  • Mastocytosis* / physiopathology
  • Mastocytosis* / therapy
  • Proto-Oncogene Proteins c-kit / genetics
  • Proto-Oncogene Proteins c-kit / immunology
  • Stem Cell Factor / genetics
  • Stem Cell Factor / immunology
  • ras Proteins / metabolism


  • Stem Cell Factor
  • Proto-Oncogene Proteins c-kit
  • ras Proteins