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UBC Theses and Dissertations

A Scid mouse model of human acute myelogenous leukemia (AML) Moore, Carolyn J. L.


A mouse model of human acute myelogenous leukemia (AML) was achieved using 400 cgy of total body irradiation of low dose 137-Cesium radiation (1.48 Rads/min.) to Scid mice which were injected intravenously with human AML cells. Demonstrated engraftment in mice of an AML cell line, M07eJ-IL-3, which harbours a retroviral construct producing human IL-3 and neomycin (G418) resistance, was determined by Southern analysis of mouse tissues for human DNA and G418 resistance of cells from mouse tissues. Nine AML peripheral blood patient samples were intravenously injected into mice following 400 cgy radiation and subsequent injections of 6 ug human interleukin-3 (IL-3) and 10 ug stem cell factor (SCF) intraperitoneally every other day. Five out of 9 patients samples engrafted in the Scid mice as assessed by DNA analysis using a human specific HERV-H probe, May-Grunwald Giemsa staining for leukemic cell morphology in mouse tissues and fluorescence in situ hybridization (FISH) for cytogenetic abnormalities in the patients. Scid-hu patient #8 demonstrated high levels of engraftment . in the bone marrow 4 weeks post injection while later time points demonstrated dissemination of the human cells in to the bone marrow, spleen, peripheral blood and tumours. These results suggest that there is heterogeneity in the degree to which patient samples will engraft if at all. This model may aid the studies of the AML stem cell biology and be useful for preclinical studies of novel therapies for this disease.

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