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PLoS One. 2013 Apr 9;8(4):e60680. doi: 10.1371/journal.pone.0060680. Print 2013.

In vivo expansion of co-transplanted T cells impacts on tumor re-initiating activity of human acute myeloid leukemia in NSG mice.

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1
Regeneration in Hematopoiesis, Center for Regenerative Therapies Dresden - CRTD, DFG Research Center and Cluster of Excellence, Technische Universität Dresden, Dresden, Germany.

Abstract

Human cells from acute myeloid leukemia (AML) patients are frequently transplanted into immune-compromised mouse strains to provide an in vivo environment for studies on the biology of the disease. Since frequencies of leukemia re-initiating cells are low and a unique cell surface phenotype that includes all tumor re-initiating activity remains unknown, the underlying mechanisms leading to limitations in the xenotransplantation assay need to be understood and overcome to obtain robust engraftment of AML-containing samples. We report here that in the NSG xenotransplantation assay, the large majority of mononucleated cells from patients with AML fail to establish a reproducible myeloid engraftment despite high donor chimerism. Instead, donor-derived cells mainly consist of polyclonal disease-unrelated expanded co-transplanted human T lymphocytes that induce xenogeneic graft versus host disease and mask the engraftment of human AML in mice. Engraftment of mainly myeloid cell types can be enforced by the prevention of T cell expansion through the depletion of lymphocytes from the graft prior transplantation.

PMID:
23585844
PMCID:
PMC3621959
DOI:
10.1371/journal.pone.0060680
[Indexed for MEDLINE]
Free PMC Article
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