This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Baskar, S. Articles by Rader, C. Search for Related Content PubMed PubMed Citation Articles by Baskar, S. Articles by Rader, C.

Unique Cell Surface Expression of Receptor Tyrosine Kinase ROR1 in Human B-Cell Chronic Lymphocytic Leukemia

Authors' Affiliations: ¹ Experimental Transplantation and Immunology Branch and ² Metabolism Branch, Center for Cancer Research, National Cancer Institute, and ³ Hematology Branch, National Heart, Lung and Blood Institute, NIH, Bethesda, Maryland

Requests for reprints: Christoph Rader, Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, NIH, 9000 Rockville Pike, Building 10 CRC, Room 3-3150, Bethesda, MD 20892-1203. Phone: 301-451-2235; Fax: 301-480-3431; E-mail: raderc{at}mail.nih.gov.

Purpose: Gene expression profiling identified receptor tyrosine kinase ROR1, an embryonic protein involved in organogenesis, as a signature gene in B-cell chronic lymphocytic leukemia (B-CLL). To assess the suitability of ROR1 as a cell surface antigen for targeted therapy of B-CLL, we carried out a comprehensive analysis of ROR1 protein expression.

Experimental Design: Peripheral blood mononuclear cells, sera, and other adult tissues from B-CLL patients and healthy donors were analyzed qualitatively and quantitatively for ROR1 protein expression by flow cytometry, cell surface biotinylation, Western blotting, and ELISA.

Results: ROR1 protein is selectively expressed on the surface of B-CLL cells, whereas normal B cells, other normal blood cells, and normal adult tissues do not express cell surface ROR1. Moreover, cell surface expression of ROR1 is uniform and constitutive, i.e., independent of anatomic niches, independent of biological and clinical heterogeneity of B-CLL, independent of B-cell activation, and found at similar levels in all B-CLL samples tested. The antibody binding capacity of B-CLL cell surface ROR1 was determined to be in the range of 10³ to 10⁴ molecules per cell. A portion of B-CLL cell surface ROR1 was actively internalized upon antibody binding. Soluble ROR1 protein was detectable in sera of <25% of B-CLL patients and a similar fraction of healthy donors at concentrations below 200 ng/mL.

Conclusions: The restricted, uniform, and constitutive cell surface expression of ROR1 protein in B-CLL provides a strong incentive for the development of targeted therapeutics such as monoclonal antibodies.

This article has been cited by other articles:

				J. W. Tyner, M. W. Deininger, M. M. Loriaux, B. H. Chang, J. R. Gotlib, S. G. Willis, H. Erickson, T. Kovacsovics, T. O'Hare, M. C. Heinrich, et al. RNAi screen for rapid therapeutic target identification in leukemia patients PNAS, May 26, 2009; 106(21): 8695 - 8700. [Abstract] [Full Text] [PDF]