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


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.

SUBMITTER: Her Z 

PROVIDER: S-EPMC5639594 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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

Her Zhisheng Z   Yong Kylie Su Mei KSM   Paramasivam Kathirvel K   Tan Wilson Wei Sheng WWS   Chan Xue Ying XY   Tan Sue Yee SY   Liu Min M   Fan Yong Y   Linn Yeh Ching YC   Hui Kam Man KM   Surana Uttam U   Chen Qingfeng Q  

Journal of hematology & oncology 20171006 1


<h4>Background</h4>Xenotransplantation of patient-derived AML (acute myeloid leukemia) cells in NOD-scid Il2rγ <sup>null</sup> (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.<h4>Methods</h4>Here, we describe an improved AML xenograft model where primary human AML c  ...[more]

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