Evidence for the involvement of a hematopoietic progenitor cell in systemic mastocytosis from single-cell analysis of mutations in the c-kit gene
- 15 July 2002
- journal article
- Published by American Society of Hematology in Blood
- Vol. 100 (2) , 661-665
- https://doi.org/10.1182/blood-2002-01-0203
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 VH/(D)/JH 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.Keywords
This publication has 16 references indexed in Scilit:
- Slowly progressive systemic mastocytosis with high mast-cell burden and no evidence of a non-mast-cell hematologic disorder: an example of a smoldering case?Leukemia Research, 2001
- A case of ‘smouldering’ mastocytosis with high mast cell burden, monoclonal myeloid cells, and C-KIT mutation Asp-816-ValLeukemia Research, 2001
- Diagnostic criteria and classification of mastocytosis: a consensus proposalLeukemia Research, 2001
- Analysis of the surface expression of c-kit and occurrence of the c-kit Asp816Val activating mutation in T cells, B cells, and myelomonocytic cells in patients with mastocytosisExperimental Hematology, 2000
- Activating and dominant inactivating c-KITcatalytic domain mutations in distinct clinical forms of human mastocytosisProceedings of the National Academy of Sciences, 1999
- Identification of Activating c-kit Mutations in Adult-, but not in Childhood-Onset Indolent Mastocytosis: A Possible Explanation for Divergent Clinical BehaviorJournal of Investigative Dermatology, 1998
- Gain-of-Function Mutations of c- kit in Human Gastrointestinal Stromal TumorsScience, 1998
- The alpha form of human tryptase is the predominant type present in blood at baseline in normal subjects and is elevated in those with systemic mastocytosis.Journal of Clinical Investigation, 1995
- Identification of a point mutation in the catalytic domain of the protooncogene c-kit in peripheral blood mononuclear cells of patients who have mastocytosis with an associated hematologic disorder.Proceedings of the National Academy of Sciences, 1995
- Identification of mutations in the coding sequence of the proto-oncogene c-kit in a human mast cell leukemia cell line causing ligand-independent activation of c-kit product.Journal of Clinical Investigation, 1993