title: In vivo expansion of co-transplanted T cells impacts on tumor re-initiating activity of human acute myeloid leukemia in NSG mice.
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.
authors.affiliation: Regeneration in Hematopoiesis, Center for Regenerative Therapies Dresden - CRTD, DFG Research Center and Cluster of Excellence, Technische Universität Dresden, Dresden, Germany.
authors.forename: Malte
authors.initials: M
authors.lastname: von Bonin
authors.forename: Martin
authors.initials: M
authors.lastname: Wermke
authors.forename: Kadriye Nehir
authors.initials: KN
authors.lastname: Cosgun
authors.forename: Christian
authors.initials: C
authors.lastname: Thiede
authors.forename: Martin
authors.initials: M
authors.lastname: Bornhauser
authors.forename: Gerard
authors.initials: G
authors.lastname: Wagemaker
authors.forename: Claudia
authors.initials: C
authors.lastname: Waskow
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D049109:Cell Proliferation; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000473:pathology*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000473:pathology*; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D022423:Myeloid Cells / Q000276:immunology / Q000473:pathology*; D009368:Neoplasm Transplantation; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology*; D018183:Transplantation Chimera; D014183:Transplantation, Heterologous / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D014916:Whole-Body Irradiation