CD117

CD117, also known as KIT or the c-KIT receptor, is a transmembrane receptor tyrosine kinase encoded by the KIT gene on chromosome 4q12. It binds the stem cell factor (SCF) and plays a key role in the development and function of several cell lineages, including hematopoietic stem and progenitor cells, mast cells, melanocytes, and the interstitial cells of Cajal.

Mechanistically, KIT activation occurs when SCF binds to the receptor, triggering dimerization and autophosphorylation. This initiates downstream signaling pathways such as PI3K-AKT, RAS-MAPK, and JAK-STAT, promoting cell survival, proliferation, and differentiation. Expression of CD117 is variable across cell types and tissues, reflecting its diverse roles in normal physiology and development.

clinically, CD117 is a widely used diagnostic marker in pathology. It is strongly expressed in gastrointestinal stromal tumors (GISTs) and supports diagnosis by immunohistochemistry. KIT mutations, particularly in exon 11, often lead to constitutive receptor activation and drive oncogenesis in many GISTs. KIT is also found in mastocytosis, some germ cell tumors (including certain seminomas), and to a lesser extent in melanomas and some leukemias.

Therapeutically, KIT signaling is a target for tyrosine kinase inhibitors. Imatinib is a commonly used first-line treatment for KIT-mutant GISTs, with second-line options such as sunitinib and other inhibitors available for resistant disease. KIT mutation status informs prognosis and treatment choices, as resistance can arise through secondary KIT mutations or alternative pathway activation.

Overall, CD117 serves as both a critical component of normal cellular signaling and a valuable diagnostic and therapeutic target in several KIT-related diseases.