Mastocytosis associated with a rare germline KIT K509I mutation displays a well-differentiated mast cell phenotype

Eunice Ching Chan, Yun Bai, Arnold S. Kirshenbaum, Elizabeth R. Fischer, Olga Simakova, Geethani Bandara, Linda M. Scott, Laura B. Wisch, Daly Cantave, Melody C. Carter, John C. Lewis, Pierre Noel, Irina Maric, Alasdair M. Gilfillan, Dean D. Metcalfe, Todd M. Wilson

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


Background Mastocytosis associated with germline KIT activating mutations is exceedingly rare. We report the unique clinicopathologic features of a patient with systemic mastocytosis caused by a de novo germline KIT K509I mutation. Objectives We sought to investigate the effect of the germline KIT K509I mutation on human mast cell development and function. Methods Primary human mast cells derived from CD34+ peripheral blood progenitors were examined for growth, development, survival, and IgE-mediated activation. In addition, a mast cell transduction system that stably expressed the KIT K509I mutation was established. Results KIT K509I biopsied mast cells were round, CD25-, and well differentiated. KIT K509I progenitors cultured in stem cell factor (SCF) demonstrated a 10-fold expansion compared with progenitors from healthy subjects and developed into mature hypergranular mast cells with enhanced antigen-mediated degranulation. KIT K509I progenitors cultured in the absence of SCF survived but lacked expansion and developed into hypogranular mast cells. A KIT K509I mast cell transduction system revealed SCF-independent survival to be reliant on the preferential splicing of KIT at the adjacent exonic junction. Conclusion Germline KIT mutations associated with mastocytosis drive a well-differentiated mast cell phenotype distinct to that of somatic KIT D816V disease, the oncogenic potential of which might be influenced by SCF and selective KIT splicing.

Original languageEnglish (US)
Pages (from-to)178-187.e1
JournalJournal of Allergy and Clinical Immunology
Issue number1
StatePublished - Jul 2014


  • K509I
  • KIT
  • germline
  • mast cells
  • mastocytosis
  • well differentiated

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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