Evaluation Of NOD-SCID-Mice for a Human B-Cell Precursor ALL Xenograft Model

To evaluate the newly bred NOD-SCID mice as recipients for human B-cell precursor ALL bone marrow or peripheral blood cells from 7 pediatric and one adult patient were transplanted onto irradiated NOD-SCID mice. Leukemic cells from 6 out of 8 patients (75%) successfully engrafted NOD-SCID mice and from 4 patients (50%) led to an extensive leukemic infiltration in the murine marrow. High level human cell engraftment could be demonstrated by flow cytometry, Southern blot analysis, PCR and cytology. By cytology and immunophenotype, the leukemia in the mice was indistinguishable from the original leukemia in the patients. Limiting dilution analysis with cells from one patient with prepre-B-ALL showed that as few as 10,000 cells were sufficient to transfer the leukemia onto NOD-SCID mice. The presence of human eosinophils in the marrow of highly engrafted mice indicated minimal coengraftment of rare residual normal cells. Development of leukemia in the mice varied between 1.5 and 7 months depending on cell dose and patient transplanted. Interestingly, conditioning of the mice by sublethal irradiation was not necessary for successful engraftment. These experiments demonstrated that NOD-SCID mice are sensitive recipients for human ALL xenografts.