Mast cell is a hematopoietic lineage dependent on Kit signaling for growth, differentiation, and survival. Mast cells are found in excessive numbers in tissues in a heterogeneous group of disorders collectively known as mastocytosis. Last decade has witnessed important advancements in our understanding of the molecular pathology of mastocytosis. First, systemic mastocytosis has been found to be associated with activating codon 816 mutations of the c-kit gene. Second, this mutation was used as a tracking marker to elucidate the clonal nature of mastocytosis. These findings have resulted in consideration of systemic mastocytosis as a clonal neoplastic disorder of a hematopoietic progenitor cell. Improved knowledge of the mechanisms causing pathological mast cell growth will lead to the discovery of novel treatment options including drugs targeting the mutated Kit protein.

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