Molecular and genetic mechanisms of mastocytosis

Abstract

Mastocytosis is a group of rare clonal disorders characterized by abnormal proliferation and accumulation of neoplastic mast cells in the skin and/or various internal organs. Molecular genetic defects play the leading role in the pathogenesis of mastocytosis despite a significant clinical and prognostic heterogeneity of different forms of this disease. In almost all forms of mastocytosis, patients carry KIT gene mutations, mostly D816V. However, these defects are observed both in forms with good prognosis and in advanced variants of the disease. Mutations in other genes, such as TET2, SRSF2, ASXL1, RUNX1, and the resulting molecular changes contribute to the clinical and pathological heterogeneity of mastocytosis and are associated with a more aggressive disease. Insight into the complexity of molecular and genetic changes in mastocytosis is essential for choosing an optimum treatment and for developing new drugs to improve the outcome of the treatment. The article described major pathogenetic mechanisms of mastocytosis and focused on the role of KIT mutations, conformation of the c-Kit receptor, and intracellular signaling pathways responsible for the proliferation of mast cells.