An improved pre-clinical patient-derived liquid xenograft mouse model for acute myeloid leukemia

An improved pre-clinical patient-derived liquid xenograft mouse model for acute myeloid leukemia
Title:
An improved pre-clinical patient-derived liquid xenograft mouse model for acute myeloid leukemia
Other Titles:
Journal of Hematology and Oncology
Keywords:
Publication Date:
06 October 2017
Citation:
Her, Z., Yong, K.S.M., Paramasivam, K. et al. An improved pre-clinical patient-derived liquid xenograft mouse model for acute myeloid leukemia. J Hematol Oncol 10, 162 (2017). https://doi.org/10.1186/s13045-017-0532-x
Abstract:
Background Xenotransplantation of patient-derived AML (acute myeloid leukemia) cells in NOD-scid Il2rγ null (NSG) mice is the method of choice for evaluating this human hematologic malignancy. However, existing models constructed using intravenous injection in adult or newborn NSG mice have inferior engraftment efficiency, poor peripheral blood engraftment, or are difficult to construct. Methods Here, we describe an improved AML xenograft model where primary human AML cells were injected into NSG newborn pups intrahepatically. Results Introduction of primary cells from AML patients resulted in high levels of engraftment in peripheral blood, spleen, and bone marrow (BM) of recipient mice. The phenotype of engrafted AML cells remained unaltered during serial transplantation. The mice developed features that are consistent with human AML including spleen enlargement and infiltration of AML cells into multiple organs. Importantly, we demonstrated that although leukemic stem cell activity is enriched and mediated by CD34+CD117+ subpopulation, CD34+CD117− subpopulation can acquire CD34+CD117+ phenotype through de-differentiation. Lastly, we evaluated the therapeutic potential of Sorafenib and Regorafenib in this AML model and found that periphery and spleen AML cells are sensitive to these treatments, whereas BM provides a protective environment to AML. Conclusions Collectively, our improved model is robust, easy-to-construct, and reliable for pre-clinical AML studies.
License type:
http://creativecommons.org/licenses/by/4.0/
Funding Info:
This study was supported by the National Research Foundation Fellowship Singapore NRF-NRFF2017-03 to Qingfeng Chen and Joint Council Office Development Programme 1334 k00082, Agency for Science, Technology and Research (A*STAR), Singapore to Qingfeng Chen.
Description:
Article is open access
ISSN:
1756-8722
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