Analysis of ROR1 Protein Expression in Mice with Reconstituted Human Immune System Components

Area of Science:

• Immunology
• Oncology
• Hematology

Background:

• Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is an oncofetal antigen highly expressed on chronic lymphocytic leukemia (CLL) B cells.
• ROR1 expression is largely absent in normal human tissues.
• Humanized NOD-scid IL2rg-/- (huNSG) mice engrafted with human CD34+ hematopoietic progenitor cells exhibit multilineage immune cell reconstitution, including B cells with elevated CD5 expression, mimicking CLL patients.

Purpose of the Study:

• To investigate ROR1 expression on B cells within the huNSG mouse model.
• To assess the utility of huNSG mice for studying B cell malignancies and ROR1-targeted immunotherapeutics.

Main Methods:

• Flow cytometry analysis was used to detect ROR1 expression on B cells from bone marrow, spleen, and blood of huNSG mice.
• TCL-1 oncogene-transduced CD34+ cells were transplanted into neonatal NSG mice to evaluate ROR1 expression changes.

Main Results:

• ROR1 was found to be highly expressed on a subset of immature B cells in the bone marrow, spleen, and blood of huNSG mice.
• Transplantation of TCL-1-transduced cells did not increase ROR1+ B cell frequency, but one mouse developed a tumor-like mass with high ROR1+ B cells.
• The huNSG model recapitulates high CD5-expressing B cells seen in CLL patients.

Conclusions:

• HuNSG mice demonstrate ROR1 expression on B cells, particularly immature ones.
• This model system holds potential for investigating B cell malignancies like CLL.
• HuNSG mice can be utilized to evaluate novel immunotherapies targeting ROR1.