Mastocytosis is a disease of disordered mast cell proliferation. It affects all ages, both sexes, and all ethnic groups. In some cases, mastocytosis has an aggressive and ultimately fatal course. Thus, our efforts are directed to improving diagnosis and treatment; and to clarify the etiology of this disease. Most recently we have described pulmonary, abdominal, and ovarian manifestations of aggressive mastocytosis. A successful approach to treatment for aggressive disease remains elusive. However, in vitro studies demonstrate that IFN-delta-1b does suppress human mast cell growth, where Interferon alpha-2b (IFNa-2b) does not. Studies on c-kit and the relevance of activating mutations which we first dentified (Asp816Val; Asp816Tyr)in mastocytosis patients are continuing. Data now indicates all patients with mastocytosis and an associated hematologic disorder have the point mutation Asp816Val in peripheral blood mononuclear cells. In contrast, adult patients with indolent mastocytosis may demonstrate this mutation only in skin lesions. Molecular studies are consistent with the conclusion that the Asp816 Val mutation is a somatic mutation and is not in germ line tissues. There is no consistent chromosomal abnormality in mastocytosis. However, cytogenic abnormalities are more frequent in aggressive disease and in those whose PBMC's show the Asp816Val mutaion. We have also now found that the Asp816Val mutation may be identified in CD34+ cells and is variably expressed in mast cells, meutrophils, monocytes, and lymphocytes.
| 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 |
Showing the most recent 10 out of 65 publications
