title: 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.
abstract: BACKGROUND
  Systemic mastocytosis is characterized by mast cell infiltration of bone marrow and tissues in the absence of identified circulating bone marrow-derived progenitors. A 58-year-old man was first seen with aggressive systemic mastocytosis manifested by urticaria pigmentosa, hepatosplenomegaly, generalized bone lesions, anemia, thrombocytopenia, monoclonal gammopathy, and increased urine histamine levels.
  
  
  OBJECTIVE
  A rapidly progressive anemia and thrombocytopenia dictated a splenectomy. We sought to identify the mast cell progenitors in the peripheral blood and to provide evidence of their maturation in tissues with immunohistochemical and ultrastructural analyses.
  
  
  RESULTS
  The peripheral blood contained 1% to 3% nonmetachromatic mononuclear cells with eccentric nuclei that expressed the mast cell proteases, tryptase and carboxypeptidase A, along with c-kit, stem cell factor (SCF), and high-affinity IgE receptor (Fc epsilon RI), but not chymase. Similar mononuclear cells colocalized in the spleen and lymph nodes with mature, metachromatic mast cells that expressed tryptase, chymase, carboxypeptidase A, c-kit, SCF, and Fc epsilon RI. Electron microscopy disclosed, at each site, a mature mast cell population with electron-dense, scroll-poor granules.
  
  
  CONCLUSIONS
  The peripheral blood of a patient with aggressive systemic mastocytosis contained immature mononuclear cells of the mast cell lineage that express c-kit, SCF, tryptase, carboxypeptidase A, and Fc epsilon RI. These cells were also found in the skin, spleen, and lymph nodes where they presumably expand, differentiate, and mature, assuming the mast cell phenotype for those tissues characterized by metachromasia, expression of a full range of mast cell-related secretory granule proteases, and ultrastructural appearance. The presence of SCF on the surface membrane of the circulating, highly immature mast cells suggests an autocrine regulation of the c-kit-SCF interaction.
authors.affiliation: Department of Medicine, Harvard Medical School, Boston, MA, USA.
authors.forename: M C
authors.initials: MC
authors.lastname: Castells
authors.forename: D S
authors.initials: DS
authors.lastname: Friend
authors.forename: C A
authors.initials: CA
authors.lastname: Bunnell
authors.forename: X
authors.initials: X
authors.lastname: Hu
authors.forename: M
authors.initials: M
authors.lastname: Kraus
authors.forename: R T
authors.initials: RT
authors.lastname: Osteen
authors.forename: K F
authors.initials: KF
authors.lastname: Austen
mesh_terms: D002454:Cell Differentiation; D002455:Cell Division; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology; D008297:Male; D008407:Mast Cells / Q000166:cytology* / Q000378:metabolism; D008415:Mastocytosis / Q000097:blood*; D008875:Middle Aged; D012867:Skin / Q000166:cytology; D013154:Spleen / Q000166:cytology; D019089:Stem Cell Factor / Q000097:blood*
chemical_list: D019089:Stem Cell Factor