KIT and mastocytosis
Graduate School of Biomedical Sciences; Department of Biochemistry and Molecular Biology; Program in Molecular Medicine
Medical Subject Headings
1-Phosphatidylinositol 3-Kinase; Amino Acid Substitution; Animals; Gametogenesis; Germ-Line Mutation; Hematopoiesis; Humans; Mast Cells; Mastocytosis; Mutation, Missense; Piebaldism; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-kit; Signal Transduction
Life Sciences | Medicine and Health Sciences
KIT is a receptor tyrosine kinase that is functionally relevant for hematopoiesis, mast cell development and function, gametogenesis and melanogenesis. Normal KIT signaling requires binding to stem cell factor, and PI3K-Akt is one of the putative effector pathways. In humans, germline loss-of-function KIT mutations have been associated with piebaldism - an autosomal dominant condition characterized by depigmented patches of skin and hair. Gain-of-function KIT mutations are usually acquired and have been associated with myeloid malignancies including core binding factor acute myeloid leukemia and systemic mastocytosis (SM), germ cell tumors, gastrointestinal stromal tumors and sinonasal T cell lymphomas. KITD816V is the most prevalent KIT mutation in mast cell disease and occurs in more than 90% of the cases that fulfill the World Health Organization diagnostic criteria for SM. However, its precise pathogenetic contribution is not well understood. In clinical practice, SM is considered either indolent or aggressive depending on the respective absence or presence of symptomatic target organ dysfunction aside from skin disease. In general, conventional therapy for SM is suboptimal, and efforts are under way to develop and employ small molecule drugs that target mutant KIT.
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Citation: Acta Haematol. 2008;119(4):194-8. Epub 2008 Jun 20. Link to article on publisher's site
Lim, Ken-Hong; Pardanani, Animesh Dev; and Tefferi, Ayalew, "KIT and mastocytosis" (2008). GSBS Student Publications. 1523.