Mastocytosis associated with a rare germlineKITK509I mutation displays a well-differentiated mast cell phenotype

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Mastocytosis associated with germlineKITactivating mutations is exceedingly rare. We report the unique clinicopathologic features of a patient with systemic mastocytosis caused by ade novogermlineKITK509I mutation.


We sought to investigate the effect of the germlineKITK509I mutation on human mast cell development and function.


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 theKITK509I mutation was established.


KITK509I biopsied mast cells were round, CD25−, and well differentiated.KITK509I 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.KITK509I 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 ofKITat the adjacent exonic junction.


GermlineKITmutations associated with mastocytosis drive a well-differentiated mast cell phenotype distinct to that of somaticKITD816V disease, the oncogenic potential of which might be influenced by SCF and selectiveKITsplicing.

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