THE PRESENCE OF MEMBRANE-BOUND STEM-CELL FACTOR ON HIGHLY IMMATURE NONMETACHROMATIC MAST-CELLS IN THE PERIPHERAL-BLOOD OF A PATIENT WITH AGGRESSIVE SYSTEMIC MASTOCYTOSIS

Background: Systemic mastocytosis is characterized by mast cell infilt ration of bone marrow and tissues in the absence of identified circula ting bone marrow-derived progenitors. A 58-year-old man was first seen with aggressive systemic mastocytosis manifested by urticaria pigment osa, hepatosplenomegaly, generalized bone lesions, anemia, thrombocyto penia, monoclonal gammopathy, and increased urine histamine levels. Ob jectives and Methods: A rapidly progressive anemia and thrombocytopeni a dictated a splenectomy. We sought to identify the mast cell progenit ors in the peripheral blood and to provide evidence of their maturatio n in tissues with immunohistochemical and ultrastructural analyses. Re sults: The peripheral blood contained 1% to 3% nonmetachromatic mononu clear cells with eccentric nuclei that expressed the mast cell proteas es, tryptase and carboxypeptidase A, along with c-kit, stem cell facto r (SCF) and high-affinity IgE receptor (Fc epsilon RI), but not chymas e. Similar mononuclear cells colocalized in the spleen and lymph nodes with mature, metachromatic mast cells that expressed tryptase, chymas e, carboxypeptidase A, c-kit, SCF, and Fc epsilon RI. Electron microsc opy disclosed at each site, a mature mast cell population with electro n-dense scroll-poor granules. Conclusions: The peripheral blood of a p atient with aggressive systemic mastocytosis contained immature mononu clear cells of the mast cell lineage that express c-kit, SCF, tryptase , carboxypeptidase A, and Fc epsilon RI. These cells were also found i n the skin, spleen, and lymph nodes where they presumably expand, diff erentiate, and mature, assuming the mast cell phenotype for those tiss ues characterized by metachromasia, expression of a full range of mast cell-related secretory granule proteases, and ultrastructural appeara nce. The presence of SCF on the surface membrane of the circulating hi ghly immature mast cells suggests an autocrine regulation of the c-kit -SCF interaction.