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

• Published in: Leukemia research 2011-10, Vol.35 (10), p.1360-1366
• Main Authors: Uhrmacher, Sabrina, Schmidt, Christina, Erdfelder, Felix, Poll-Wolbeck, Simon Jonas, Gehrke, Iris, Hallek, Michael, Kreuzer, Karl-Anton
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Antibodies - analysis; Antigens, CD - immunology; Antigens, CD - metabolism; B-Lymphocytes - metabolism; B-Lymphocytes - pathology; Biomarkers - analysis; Case-Control Studies; Chronic lymphocytic leukemia; Female; Flow Cytometry; Follow-Up Studies; Hematology, Oncology and Palliative Medicine; Humans; Leukemia, Lymphocytic, Chronic, B-Cell - diagnosis; Leukemia, Lymphocytic, Chronic, B-Cell - immunology; Leukemia, Lymphocytic, Chronic, B-Cell - metabolism; Leukemia, Lymphocytic, Chronic, B-Cell - pathology; Lymphoma, B-Cell - diagnosis; Lymphoma, B-Cell - immunology; Lymphoma, B-Cell - metabolism; Lymphoma, B-Cell - pathology; Male; Middle Aged; Minimal residual disease; Receptor tyrosine kinase-like orphan receptor 1; Receptor Tyrosine Kinase-like Orphan Receptors - analysis; Receptor Tyrosine Kinase-like Orphan Receptors - biosynthesis; Reverse Transcriptase Polymerase Chain Reaction; Sensitivity and Specificity
• ISSN: 0145-2126; 1873-5835
• DOI: 10.1016/j.leukres.2011.04.006

Abstract 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.