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

E Saland (1, 2) , H Boutzen (1, 2) , R Castellano (3) , L Pouyet (3) , E Griessinger (4) , C Larrue (1, 2) , F de Toni (1, 2) , S Scotland (1, 2) , Mathieu David (1, 2) , G Danet-Desnoyers (5) , F Vergez (1, 2) , Y Barreira (6) , Yves Collette (3) , C Récher (7, 1, 2) , J-E Sarry (1, 2)

1 CRCT - Centre de Recherches en Cancérologie de Toulouse
2 IUT de Tarbes
3 CRCM - Centre de Recherche en Cancérologie de Marseille
4 C3M - Centre méditerranéen de médecine moléculaire
5 Department of Medicine
6 Service d'Expérimentation Animale
7 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse

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 IL2R gamma(null)(c) 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.

Mots clés: IMMUNODEFICIENT MICE; NOD/SCID MICE; CELLS; TRANSPLANTATION; HEMATOPOIESIS; IRRADIATION; ENGRAFTMENT; BUSULFAN

Domaines: Cancer

E Saland, H Boutzen, R Castellano, L Pouyet, E Griessinger, et al.. A robust and rapid xenograft model to assess efficacy of chemotherapeutic agents for human acute myeloid leukemia. Blood Cancer Journal, 2015, 5 (e297), ⟨10.1038/bcj.2015.19⟩. ⟨hal-01219119⟩