title: Evidence for the involvement of a hematopoietic progenitor cell in systemic mastocytosis from single-cell analysis of mutations in the c-kit gene.
abstract: Mast cells are derived from multipotential hematopoietic progenitors and are clonally increased in systemic mastocytosis, a disease associated with point mutations of codon 816 (most commonly Asp816Val) of c-kit. To study the lineage relationship and the extent of expansion of cells derived from the mutated clone, we examined the occurrence of the Asp816Val c-kit mutation in genomic DNA of individual sorted peripheral blood T cells, B cells, and monocytes in patients with indolent systemic mastocytosis. The mutation was detected in varying frequencies in the genomic DNA of individual B cells and monocytes and bone marrow mast cells in patients with extensive disease. In B cells, the immunoglobulin repertoire was polyclonal, indicating that the mutation occurred before V(H)/(D)/J(H) recombination. These results show that mastocytosis is a disorder of a pluripotential hematopoietic progenitor cell that gives rise to B cells and monocytes in addition to mast cells and that the affected clone shows variable expansion in these lineages in the peripheral blood of patients with systemic mastocytosis.
authors.affiliation: Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), and Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: A Selim
authors.initials: AS
authors.lastname: Yavuz
authors.forename: Peter E
authors.initials: PE
authors.lastname: Lipsky
authors.forename: Sule
authors.initials: S
authors.lastname: Yavuz
authors.forename: Dean D
authors.initials: DD
authors.lastname: Metcalfe
authors.forename: Cem
authors.initials: C
authors.lastname: Akin
mesh_terms: D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D019070:Cell Lineage; D002999:Clone Cells / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D007962:Leukocytes / Q000201:enzymology / Q000473:pathology; D008297:Male; D008415:Mastocytosis / Q000209:etiology / Q000235:genetics / Q000473:pathology*; D008875:Middle Aged; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*
chemical_list: D019009:Proto-Oncogene Proteins c-kit