Evidence for the involvement of a hematopoietic progenitor cell in systemic mastocytosis from single-cell analysis of mutations in the c-kit gene

Blood. 2002 Jul 15;100(2):661-5. doi: 10.1182/blood-2002-01-0203.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Amino Acid Substitution
  • Cell Lineage
  • Clone Cells / enzymology
  • Clone Cells / metabolism
  • Clone Cells / pathology
  • DNA Mutational Analysis
  • Female
  • Gene Frequency
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / physiology*
  • Humans
  • Leukocytes / enzymology
  • Leukocytes / pathology
  • Male
  • Mastocytosis / etiology
  • Mastocytosis / genetics
  • Mastocytosis / pathology*
  • Middle Aged
  • Point Mutation*
  • Polymorphism, Single Nucleotide
  • Proto-Oncogene Proteins c-kit / genetics*


  • Proto-Oncogene Proteins c-kit