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Blood Cancer J. 2015 Mar 20;5:e297. doi: 10.1038/bcj.2015.19.

A robust and rapid xenograft model to assess efficacy of chemotherapeutic agents for human acute myeloid leukemia.

Author information

1
1] Cancer Research Center of Toulouse, INSERM, U1037, Toulouse, France [2] University of Toulouse, Toulouse, France.
2
1] Cancer Research Center of Marseille, INSERM, U1068, Marseille, France [2] Institut Paoli-Calmettes, Marseille, France [3] Aix-Marseille Université, Marseille, France [4] CNRS, UMR7258, Marseille, France.
3
1] Centre Méditerranéen de Médecine Moléculaire, INSERM, U1065, Nice, France [2] Université de Nice Sophia Antipolis, Nice, France.
4
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
5
Service d'Expérimentation Animale, UMS006, 31059, Toulouse cedex, France.
6
1] Cancer Research Center of Toulouse, INSERM, U1037, Toulouse, France [2] University of Toulouse, Toulouse, France [3] Département d'Hématologie, Centre Hospitalier Universitaire de Toulouse, Institut Universitaire du Cancer Toulouse Oncopole, Toulouse cedex, France.

Abstract

Relevant preclinical mouse models are crucial to screen new therapeutic agents for acute myeloid leukemia (AML). Current in vivo models based on the use of patient samples are not easy to establish and manipulate in the laboratory. Our objective was to develop robust xenograft models of human AML using well-characterized cell lines as a more accessible and faster alternative to those incorporating the use of patient-derived AML cells. Five widely used AML cell lines representing various AML subtypes were transplanted and expanded into highly immunodeficient non-obese diabetic/LtSz-severe combined immunodeficiency IL2Rγc(null) mice (for example, cell line-derived xenografts). We show here that bone marrow sublethal conditioning with busulfan or irradiation has equal efficiency for the xenotransplantation of AML cell lines. Although higher number of injected AML cells did not change tumor engraftment in bone marrow and spleen, it significantly reduced the overall survival in mice for all tested AML cell lines. On the basis of AML cell characteristics, these models also exhibited a broad range of overall mouse survival, engraftment, tissue infiltration and aggressiveness. Thus, we have established a robust, rapid and straightforward in vivo model based on engraftment behavior of AML cell lines, all vital prerequisites for testing new therapeutic agents in preclinical studies.

PMID:
25794133
PMCID:
PMC4382660
DOI:
10.1038/bcj.2015.19
[Indexed for MEDLINE]
Free PMC Article

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