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

Abstract EN

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.