Please use this identifier to cite or link to this item: https://doi.org/10.1186/s13045-017-0532-x
Title: An improved pre-clinical patient-derived liquid xenograft mouse model for acute myeloid leukemia
Authors: Her Z.
Yong K.S.M.
Paramasivam K.
Tan W.W.S.
Chan X.Y.
Tan S.Y.
Liu M. 
Fan Y.
Linn Y.C. 
Hui K.M. 
Surana U. 
Chen Q. 
Keywords: regorafenib
sorafenib
stem cell factor receptor
acute myeloid leukemia
acute myeloid leukemia cell line
animal cell
animal experiment
animal model
animal tissue
Article
blood analysis
bone marrow
CD34 selection
cell activity
cell differentiation
cell infiltration
cell subpopulation
disease course
drug screening
drug sensitivity
engraftment
human
human cell
mouse
nonhuman
phenotype
preclinical study
primary cell line
spleen
splenomegaly
therapy effect
transplantation
tumor xenograft
acute myeloid leukemia
animal
disease model
genetics
nonobese diabetic mouse
pathology
procedures
SCID mouse
xenograft
Animals
Disease Models, Animal
Humans
Leukemia, Myeloid, Acute
Mice
Mice, Inbred NOD
Mice, SCID
Transplantation, Heterologous
Issue Date: 2017
Citation: Her Z., Yong K.S.M., Paramasivam K., Tan W.W.S., Chan X.Y., Tan S.Y., Liu M., Fan Y., Linn Y.C., Hui K.M., Surana U., Chen Q. (2017). An improved pre-clinical patient-derived liquid xenograft mouse model for acute myeloid leukemia. Journal of Hematology and Oncology 10 (1) : 162. ScholarBank@NUS Repository. https://doi.org/10.1186/s13045-017-0532-x
Abstract: Background: Xenotransplantation of patient-derived AML (acute myeloid leukemia) cells in NOD-scid Il2r? 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. © 2017 The Author(s).
Source Title: Journal of Hematology and Oncology
URI: https://scholarbank.nus.edu.sg/handle/10635/173769
ISSN: 17568722
DOI: 10.1186/s13045-017-0532-x
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