The mast cell precursor in human peripheral blood is CD34+/FcepsilonRI-. The number of mast cells arising per CD34+ cell in culture is greater when the CD34+ cells are obtained from patients with mastocytosis with a hematologic disorder compared to normal subjects. This observation led us to search for mutations in the receptor for SCF, c-kit, which would result in enhanced cell proliferaton. Using SSCP analysis of PCR products, and genomic DNA analysis, we identified a mutation in c-kit which has been reported in murine and human mast cell lines to result in increased mast cell proliferation. This mutation was associated with mastocytosis in which a hematologic disorder was also present and which exhibited predominantly myelodysplastic features. This mutation was not identified in 67 normal subjects, or in patients with agressive mastocytosis, and was usually absent in patients with indolent mastocytosis. Interferon alpha-2b was administered to 3 patients with progressive forms of mastocytosis for periods in excess of one year. All patients demonstrated continued progression of disease in spite of interferon alpha-2b adminis-tration. Mast cell tryptase in the serum of patients with mastocytosis differs from the tryptase released during anaphylaxis. This difference is recognized by specific monoclonal antibodies and may provide an improved means to follow disease progression and response to theapy. The tryptase found in the sera of mastocytosis is, however, identical to the tryptase found in the sera of patients not experiencing mast cell degranulation, i.e. the """"""""resting tryptase"""""""".
| Akin, Cem; Valent, Peter; Metcalfe, Dean D (2010) Mast cell activation syndrome: Proposed diagnostic criteria. J Allergy Clin Immunol 126:1099-104.e4 |
| Kulka, Marianna; Metcalfe, Dean D (2010) Isolation of tissue mast cells. Curr Protoc Immunol Chapter 7:Unit 7.25 |
| Lahortiga, Idoya; Akin, Cem; Cools, Jan et al. (2008) Activity of imatinib in systemic mastocytosis with chronic basophilic leukemia and a PRKG2-PDGFRB fusion. Haematologica 93:49-56 |
| Simons, F E R; Frew, A J; Ansotegui, I J et al. (2008) Practical allergy (PRACTALL) report: risk assessment in anaphylaxis. Allergy 63:35-7 |
| Peavy, Richard D; Metcalfe, Dean D (2008) Understanding the mechanisms of anaphylaxis. Curr Opin Allergy Clin Immunol 8:310-5 |
| Maric, Irina; Robyn, Jamie; Metcalfe, Dean D et al. (2007) KIT D816V-associated systemic mastocytosis with eosinophilia and FIP1L1/PDGFRA-associated chronic eosinophilic leukemia are distinct entities. J Allergy Clin Immunol 120:680-7 |
| Valent, P; Akin, C; Metcalfe, D D (2007) FIP1L1/PDGFRA is a molecular marker of chronic eosinophilic leukaemia but not for systemic mastocytosis. Eur J Clin Invest 37:153-4 |
| Simons, F Estelle R; Frew, Anthony J; Ansotegui, Ignacio J et al. (2007) Risk assessment in anaphylaxis: current and future approaches. J Allergy Clin Immunol 120:S2-24 |
| Valent, P; Akin, C; Escribano, L et al. (2007) Standards and standardization in mastocytosis: consensus statements on diagnostics, treatment recommendations and response criteria. Eur J Clin Invest 37:435-53 |
| Jensen, Bettina M; Metcalfe, Dean D; Gilfillan, Alasdair M (2007) Targeting kit activation: a potential therapeutic approach in the treatment of allergic inflammation. Inflamm Allergy Drug Targets 6:57-62 |
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