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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Bone Marrow Transplantation / immunology
  • Bone Marrow Transplantation / mortality
  • Bone Marrow Transplantation / pathology*
  • Cell Proliferation
  • Female
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / pathology*
  • Humans
  • Leukemia, Myeloid, Acute / immunology
  • Leukemia, Myeloid, Acute / pathology*
  • Lymphocyte Depletion
  • Male
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Middle Aged
  • Myeloid Cells / immunology
  • Myeloid Cells / pathology*
  • Neoplasm Transplantation
  • Survival Analysis
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology*
  • Transplantation Chimera
  • Transplantation, Heterologous / immunology
  • Transplantation, Heterologous / mortality
  • Transplantation, Heterologous / pathology*
  • Whole-Body Irradiation

Grant support

CW is supported by the CRTD - DFG Research Center for Regenerative Therapies Dresden, Technische Universität Dresden, Fetscherstraße 105, 01307 Dresden. This work was supported by a grant of the Deutsche Forschungsgemeinschaft (DFG) Research Center and Cluster of Excellence for Regenerative Therapies Dresden (CRTD) and SFB 655 (#B9, Waskow, Gerok rotation position, #B2, Bornhäuser). The project was further supported by an intramural CRTD-seed grant and a grant from the European Union FP7 CELL-PID. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.