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

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...

Full description

Saved in:
Bibliographic Details
Published in:Clinical cancer research 2008-01, Vol.14 (2), p.396-404
Main Authors: BASKAR, Sivasubramanian, KWONG, Kayin, HOFER, Thomas, LEVY, Jessica M, KENNEDY, Michael G, LEE, Elinor, STAUDT, Louis M, WILSON, Wyndham H, WIESTNER, Adrian, RADER, Christoph
Format: Article
Language:English
Subjects:
Antineoplastic agents
B-Lymphocytes - enzymology
Biological and medical sciences
Biomarkers, Tumor
Blood Cells - enzymology
Cell Line, Tumor
Cell Membrane - enzymology
cell surface antigen
Hematologic and hematopoietic diseases
Humans
leukemia
Leukemia, Lymphocytic, Chronic, B-Cell - enzymology
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Leukocytes, Mononuclear - enzymology
Medical sciences
new target
Pharmacology. Drug treatments
Receptor Protein-Tyrosine Kinases - blood
Receptor Protein-Tyrosine Kinases - metabolism
receptor tyrosine kinase
Receptor Tyrosine Kinase-like Orphan Receptors
tumor antigen
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 10 3 to 10 4 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
ISSN:1078-0432
1557-3265
DOI:10.1158/1078-0432.CCR-07-1823