SLAM family member 8 is involved in oncogenic KIT ‐mediated signalling in human mastocytosis

The signalling lymphocytic activation molecule family member 8 ( SLAMF 8)/ CD 353 is a member of the CD 2 family of proteins. Its ligand has not been identified. SLAMF 8 is expressed by macrophages and suppresses cellular functions. No study has yet explored SLAMF 8 expression or function in human mastocytosis, which features oncogenic KIT ‐mediated proliferation of human mast cells. SLAMF 8 protein was expressed in human mastocytosis cells, immunohistochemically. SLAMF 8 expression was also evident in the human mast cell lines, HMC 1.2 (expressing oncogenic KIT ) and LAD 2 (expressing wild‐type KIT ) cells. SLAMF 8 knock‐down significantly reduced the KIT ‐mediated growth of HMC 1.2 cells but not that of LAD 2 cells. SLAMF 8 knock‐down HMC 1.2 cells exhibited significant attenuation of SHP ‐2 activation and oncogenic KIT ‐mediated RAS ‐ RAF ‐ ERK signalling. An interaction between SLAMF 8 and SHP ‐2 was confirmed in HMC 1.2 cells and all pathological mastocytosis specimens examined (19 of 19 cases, 100%). Thus, SLAMF 8 is involved in oncogenic KIT ‐mediated RAS ‐ RAF ‐ ERK signalling and the subsequent growth of human neoplastic mast cells mediated by SHP ‐2. SLAMF 8 is a possible therapeutic target in human mastocytosis patients.