Regulation of normal and neoplastic human mast cell development in mastocytosis

Mastocytosis, a condition characterized by a pathologic accumulation of clonal mast cells in tissues, offers a unique opportunity to study the growth and differentiation of mast cells as well as their contribution to various pathologic processes. This is because molecular pathways governing the proliferation and survival of mast cells show striking similarities between normal mast cells and their counterparts in mastocytosis. For example, activation of Kit, a transmembrane receptor for stem cell factor (SCF) is critical for the growth and differentiation of normal mast cells. Mutations such as D816V resulting in its pathologic activation are strongly associated with mastocytosis. Treatment of mastocytosis is aimed at controlling symptoms, as no specific drug has yet been clinically demonstrated to selectively eliminate mast cells carrying the D816V gain-of-function c-kit mutation. Non-myeloablative bone marrow transplantation is performed in select patients to take advantage of the immunotherapeutic effects of the graft.