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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.

Original publication




Journal article


Journal of immunology research

Publication Date





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