Abstract
Xenotransplantation of human acute myeloid leukemia (AML) in immunocompromised animals has been critical for defining leukemic stem cells. However, existing immunodeficient strains of mice have short life spans and low levels of AML cell engraftment, hindering long-term evaluation of primary human AML biology. A recent study suggested that NOD/LtSz-scid IL2Rγc null (NSG) mice have enhanced AML cell engraftment, but this relied on technically challenging neonatal injections. Here, we performed extensive analysis of AML engraftment in adult NSG mice using tail vein injection. Of the 35 AML samples analyzed, 66% showed bone marrow engraftment over 0.1%. Further, 37% showed high levels of engraftment (>10%), with some as high as 95%. A 2–44-fold expansion of AML cells was often seen. Secondary and tertiary recipients showed consistent engraftment, with most showing further AML cell expansion. Engraftment did not correlate with French–American–British subtype or cytogenetic abnormalities. However, samples with FLT3 mutations showed a higher probability of engraftment than FLT3 wild type. Importantly, animals developed organomegaly and a wasting illness consistent with advanced leukemia. We conclude that the NSG xenotransplantation model is a robust model for human AML cell engraftment, which will allow better characterization of AML biology and testing of new therapies.
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Acknowledgements
We thank Catherine Keefer and Anthony Secreto of the Stem Cell and Xenograft Core at the University of Pennsylvania for their excellent technical assistance with NSG mice, leukemia cell injections, and animal health monitoring; Beth A Burke and Craig Jordan for critical evaluation of manuscript, design, and placement of figures; and Minu Samanta for analysis of FLT3 mutation expression in select AML samples. We also thank Neena J Panackal and Daniel Martinez from the Pathology Core Laboratories at the Children's Hospital of Philadelphia for processing mouse tissues and performing H & E stains on liver and kidney of engrafted recipients. MC was supported in part by the Leukemia Lymphoma Society of America.
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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)
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Sanchez, P., Perry, R., Sarry, J. et al. A robust xenotransplantation model for acute myeloid leukemia. Leukemia 23, 2109–2117 (2009). https://doi.org/10.1038/leu.2009.143
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DOI: https://doi.org/10.1038/leu.2009.143
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