Receptor Tyrosine Kinase Profiling Identifies RON Tyrosine Kinase in Hodgkin and Non-Hodgkin Lymphoma
BN Coffing, CC Mankey, EA Wey, S Mongia, C McNeil, DG Thomas, F Keyoumarsi, KSJ Elenitoba-Johnson, MS Lim. University of Michigan, Ann Arbor, MI; University of Utah, Salt Lake City, UT
Background: Comprehensive analysis of receptor tyrosine kinases would enhance our understanding of the pathogenesis of lymphomas. We carried out protein microarray profiling of 42 receptor tyrosine kinases (RTK) in anaplastic large cell and Hodgkin lymphoma-derived cell lines using a commercial array (Proteome Profiler Array, R&D Systems, USA). One of the RTK identified in the ALCL-derived cell line was the Met-related RTK, RON tyrosine kinase. RON was originally identified as a chemotactic factor for macrophages but also participates in the development of epithelium by driving cells to proliferate. Constitutively active variants of RON have been found in primary colon cancers and colon and gastric cancer cell lines. Expression of RON has been described in a subset of classical Hodgkin lymphoma, mediastinal B cell lymphoma and a small minority of cases of other B cell non-Hodgkin lymphomas, but only a small number of cases has been studied, and RON expression has not been evaluated in primary cases of ALCL or other T cell lymphomas. We studied RON expression in a variety of lymphomas to validate published findings in cHL and B cell NHL in a larger number of cases and characterize expression in T cell lymphomas.
Design: We built tissue microarrays of CLL/SLL, follicular lymphoma, mantle cell lymphoma, diffuse large B cell lymphoma, peripheral T cell lymphoma, not otherwise specified, ALCL and cHL and evaluated RON expression by immunohistochemistry. In reactive tonsil, T cells are negative, and germinal center cells show weak RON expression. Cases with moderate or strong cytoplasmic expression of RON are considered positive.