Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is an oncofetal antigen expressed on multiple tumors and has no significant expression on normal human tissues. ROR1 is highly upregulated in chronic lymphocytic leukemia (CLL) B cells. NOD-scid IL2rg-/- (NSG) mice engrafted with human CD34+ hematopoietic progenitor cells (huNSG) achieved multilineage human immune cell reconstitution including B cells, T cells, NK cells, and DCs. Like the CLL patients, huNSG mice have abnormally high percentage of CD5-expressing B cells in the periphery. In light of this, we aim to determine whether ROR1 is expressed on huNSG B cells. Using flow cytometry analysis, we found that ROR1 was highly expressed in a proportion of bone marrow, spleen, and blood B cells, which were mostly immature B cells. Transplantation of the oncogene TCL-1-transduced CD34+ cells in neonatal NSG mice did not increase the frequency of ROR1-expressing B cells, but the mouse with the highest engraftment of transduced cells developed a tumor-like lump consisting of a high percentage of ROR1-expressing B cells. This study highlights the potential use of huNSG mice to study B cell malignant diseases and to evaluate immunotherapeutics targeting ROR1.
Journal of immunology research
Department of Hematology, University College London Cancer Institute, University College London, London, UK.
B-Lymphocytes, Hematopoietic Stem Cells, Animals, Transplantation Chimera, Mice, Knockout, Humans, Mice, Mice, SCID, Proto-Oncogene Proteins, Antigens, CD34, Immunotherapy, Hematopoietic Stem Cell Transplantation, Flow Cytometry, Cell Separation, Gene Expression Regulation, Neoplastic, Up-Regulation, Interleukin Receptor Common gamma Subunit, Leukemia, Lymphocytic, Chronic, B-Cell, Receptor Tyrosine Kinase-like Orphan Receptors, Carcinogenesis