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Mast Cell Disease
Pathophysiology
Mast cells are derived from pluripotent and committed hematopoietic progenitors present in bone marrow and peripheral blood.
The production and regulation of mast cells are complex, as is the etiology of mast cell disease. There is a growing understanding, though, of the molecular basis of the disorder. A specific receptor for stem cell factor—tyrosine kinase KIT—is expressed on the surface of mast cells, and the interaction between stem cell factor and KIT is an essential regulator of mast cell growth and development.1,2 Binding of stem cell factor to KIT activates tyrosine kinase activity, which in turn causes downstream signaling that results in normal mast cell proliferation and differentiation. Dysregulation of KIT signaling has been associated with systemic mastocytosis.2 In addition, the FIP1L1-PDGFRA fusion gene (the molecular abnormality causing the constitutive tyrosine kinase activity associated with the myeloproliferative form of hypereosinophilic syndrome, or HES) has been identified in patients with systemic mastocytosis accompanied by eosinophilia.
The systemic manifestations of mast cell disease are believed to be due to release of mast cell-derived mediators including histamine, prostaglandins, heparin, neutral proteases, and acid hydrolases.3 Symptoms and signs associated with these mediators may include headache, flushing, dizziness, tachycardia, hypotension, syncope, anorexia, nausea, vomiting, abdominal pain, and diarrhea. Complications in the skeletal, hematopoietic, gastrointestinal, cardiopulmonary, and central nervous systems may be due directly to mast cell infiltration or to mast cell mediator release.3
References:
- Longley BJ, Jr, Metcalfe DD, Tharp M, et al. Activating and dominant inactivating c-KIT catalytic domain mutations in distinct clinical forms of human mastocytosis. Proc Natl Acad Sci U S A. 1999;96:1609-1614.
- Longley BJ, Jr, Reguera MJ, Ma Y. Classes of c-KIT activating mutations: proposed mechanisms of action and implications for disease classification and therapy. Leuk Res. 2001;25:571-576.
- Hogan D. Mastocytosis. Available at: http://www.emedicine.com/derm/topic258.htm. Accessed April 23, 2006.
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