Use of the receptor tyrosine kinase-like orphan receptor 1 (ROR1) as a diagnostic tool in chronic lymphocytic leukemia (CLL).

Flow cytometry is commonly used to establish the diagnosis of chronic lymphocytic leukemia (CLL). A defined combination of antibodies discriminates between normal B cells and CLL cells (coexpression of CD5, CD19, and CD23). The receptor tyrosine-like orphan receptor one (ROR1) is an embryonic glycoprotein involved in several developmental processes. It was shown to be highly and specifically expressed on circulating B lymphoma cells, but not on normal B cells. Here, we examined the potential of ROR1 as a diagnostic marker in initial and follow-up diagnostics of patients with CLL. 105 untreated and 72 treated patients, as well as healthy volunteers were examined using flow cytometry assays. Furthermore, we examined 10 patients with various B cell non-Hodgkin lymphomas (B-NHL). ROR1 was detected using a directly labeled antibody. We detected uniformly high ROR1 expression levels in all CLL samples. In marked contrast, only low or absent ROR1 expression levels were found on B cells from healthy donors. ROR1 expression in CLL patients was not influenced by various treatments. Taken together, ROR1 may be used as a diagnostic marker for CLL. As it is the only antigen which can exclusively be detected on neoplastic B cells it may greatly increase both, specificity as well as sensitivity, in lymphoma diagnostics.