In order to study human acute B-lymphoblastic leukemia (B-ALL) in vivo, a novel xenotransplant model was established by using neonatal NOD/SCID/IL2 receptor γ chain(null) mouse. The CD34(+)CD19(+) bone marrow (BM) cells were sorted from the CD3(-)CD4(-)CD8(-) fraction of B-ALL patients by fluorescence-activated cell sorting (FACS), and injected into 100 cGy irradiated neonatal NOD/SCID/IL2rγ(null) mice through facial vein. The engraftment and proliferation of human B-ALL cells were monitored by the presence of human CD45(+)CD19(+) cells in peripheral blood (PB). Human hematopoietic chimerism in PB, BM and spleen of the recipients was examined by multiparameter flow cytometry. Morphological analyses of FACS-sorted murine marrow cells were performed by using May-Grunwald-Giemsa staining. Furthermore, leukemia cell infiltration in the organs was evaluated by hematoxylin-eosin staining. The results indicated that the sorted CD34(+)CD19(+) cells were able to initiate human B-ALL in vivo. The percentages of human CD45(+)CD19(+) cells in PB, BM and spleen of the recipient mice were (83.36 ± 10.05)%, (93.88 ± 5.05)% and (88.31 ± 5.01)%, respectively. Furthermore, the phenotype and morphology of the engrafted human cells were resemble to the original B-ALL cells from the patients. Similar to the clinical features, transplanted leukemic cells infiltrated into the organs, such as liver, lung, kidney and brain in the recipients. It is concluded that neonatal NOD/SCID/IL2rγ(null) mice can support efficient engraftment of the sorted CD34(+)CD19(+) cells from human B-ALL for a long-term period. Human-mouse xenotransplant model using neonatal NOD/SCID/IL2rγ(null) mouse may provide an important system to study the biology of human B-ALL in vivo.
Animals ; Animals, Newborn ; Disease Models, Animal ; Humans ; Interleukin-2 Receptor alpha Subunit ; immunology ; Male ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Neoplasm Transplantation ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; immunology