We have initiated a project in collaboration with Dr. Dean Metcalfe of the National Institute of Allergy and Infectious Diseases to study patients with systemic mastocytosis.? Systemic mastocytosis is a rare myeloproliferative disorder characterized by abnormal accumulation of mast cells in one or more organ systems. Recent data indicate that it is a clonal disorder of mast cells demonstrating somatic mutations in KIT, the proto-oncogene that encodes a tyrosine kinase receptor for stem cell factor. We are prospectively studying patients undergoing evaluation for mast cell disease. Laboratory evaluation includes: (1) morphologic review of bone marrow biopsies and aspirates, (2) molecular testing for the presence of the KIT mutation and (3) immunophenotypic analysis of mast cells and other hematopoietic elements by flow cytometry. Patients diagnosed with systemic mastocytosis are followed over time. As novel treatments for this rare disease become available, patient responses to different therapies will be evaluated. During last year, we have developed RT-PCR/RFLP assay for detection of the most prevalent KIT mutation in mastocytosis patients (KIT D816V). We have also developed a flow cytometric assay for immunophenotypic analysis of mast cells, since it has been recently described that neoplastic mast cells display some unique aberrant immunophenotypic characteristics, most notably, aberrantly express CD2 and/or CD25. So far, the results of our analysis (total of 46 patients) show complete concordance between diagnosis of systemic mastocytosis, the presence of KIT D816V point mutation, and aberrant expression of CD25 antigen on mast cells. Expression of CD2 antigen on mast cells was detected in only 57% of patients with systemic mastocytosis. Aberrant expression of CD25 and CD2 was not detected in normal marrow mast cells. One abstract is published.
| 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 |
