GOOD ENGRAFTMENT OF B-CELL PRECURSOR ALL IN NOD-SCID MICE

Background In vivo models for human B cell precursor ALL have been est ablished by transplanting human leukemic cells onto immune-deficient S CID mice. High risk and relapsed leukemias engraft very well in these mice, however, good prognosis pediatric ALL often grow poorly if at al l. Recently a new, even more immune-deficient mouse strain has been br ed by crossing the scid mutation onto the NOD mouse background. As the se NOD-SCID mire have been shown to be better recipients for human mye loid cells the goal of this study was to test these mice as hosts for human acute lymphoblastic leukemia cells. Patients and methods Bone ma rrow or peripheral blood cells from 7 pediatric and one adult patient with B-cell precursor ALL were transplanted onto immune-deficient NOD- SCID mice according to established protocols. Main results ALL cells f rom 6 out of the 8 patients (75%) successfully engrafted the NOD-SCID mice and from 4 patients (50%) led to an extensive leukemic infiltrati on in the murine marrow (>10%). High level human cell engraftment coul d be demonstrated. by flow cytometry, Southern blot analysis and cytol ogy. By cytology and immunophenotype the leukemia in the mice was indi stinguishable from the original leukemia in the patients, The presence of few human eosinophils in the marrow of highly engrafted mice indic ates minimal coengraftment of residual normal cells. Development of ov ert leukemia in the mice after transplantation of cells from different patients varied between 1.5 and 7 months. Interestingly and in contra st to myeloid cells, conditioning of the mice by sublethal irradiation was not necessary for successful engraftment. Limiting dilution exper iments with leukemic blasts from one patient showed that as few as 10 000 cells were sufficient to transfer the leukemia onto NOD-SCID mice. Conclusions NOD-SCID mice are sensitive recipients for human ALL xeno grafts.