Mastocytosis.
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.
Metcalfe
Dean D
DD
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
D000818:Animals; D006801:Humans; D008407:Mast Cells / Q000276:immunology*; D008415:Mastocytosis / Q000145:classification / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000276:immunology; D019089:Stem Cell Factor / Q000235:genetics / Q000276:immunology; D018631:ras Proteins / Q000378:metabolism
D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit; D018631:ras Proteins