Mastocytosis is a disorder characterized by pathologic accumulation of mast cells in tissues, most commonly in skin and bone marrow. In order to assess whether skin involvement is predictive of bone marrow (systemic) disease, 67 patients were examined in a prospective study. Results revealed that an examination of the extent and density of skin lesions helps identify those with more extensive bone marrow disease with poorer prognostic features and require a more thorough evaluation. Skin lesions of mastocytosis (also termed urticaria pigmentosa), however, may decrease in intensity or regress in a small subset of patients. Another study reported 12 such patients who experienced regression of urticaria pigmentosa and analyzed the clinical correlates of this observation. It was found that old age and co-existence of another hematologic disorder were associated with apparent improvement of skin lesions in patients with mastocytosis. Activating mutations in the c-kit protooncogene codon 816 are found in most patients with systemic mastocytosis involving the bone marrow. Since c-kit encodes a transmembrane receptor tyrosine kinase, inhibition of this pathway by drugs such as imatinib (Gleevec) has been evaluated as a potential therapeutic strategy in mast cell disease. Using primary mast cells obtained from patient bone marrow aspirates, Gleevec has been shown to exert a potent cytotoxic activity on mast cells carrying c-kit with a wild-type codon 816. On the other hand, the drug was ineffective in killing mast cells carrying a codon 816 c-kit mutation. To complement these observations, a patient with a previously undescribed variant of mastocytosis was found to have a novel activating mutation in the transmembrane portion of c-kit, and showed a dramatic response to imatinib. Nevertheless, current treatment options for patients carrying codon 816 c-kit mutations are limited and clinical trials are needed to assess response to investigational therapies. In order to help interpretation of these future clinical trials, standardized response criteria were formulated in collaboration with other researchers in the field. Finally, pathologic mast cells may be encountered in other bone marrow disorders such as hypereosinophilic syndromes. Flow cytometric characterization of mast cells in patients with HES revealed mast cells to have unique surface phenotypes in a subset of patients with this disorder who have myeloproliferative features and respond to therapy with imatinib.
| 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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