Transgenic expression of human cytokines in immunodeficient mice does not facilitate myeloid expansion of BCR-ABL1 transduced human cord blood cells

Maria Askmyr, Sofia Von Palffy, Nils Hansen, Niklas Landberg, Carl Högberg, Marianne Rissler, Helena Ågerstam, Thoas Fioretos

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

3 Citeringar (SciVal)

Sammanfattning

Several attempts have been made to model chronic myeloid leukemia (CML) in a xenograft setting but expansion of human myeloid cells in immunodeficient mice has proven difficult to achieve. Lack of cross-reacting cytokines in the microenvironment of the mice has been proposed as a potential reason. In this study we have used NOD/SCID IL2–receptor gamma deficient mice expressing human SCF, IL-3 and GM-CSF (NSGS mice), that should be superior in supporting human, and particularly, myeloid cell engraftment, to expand BCR-ABL1 expressing human cells in order to model CML. NSGS mice transplanted with BCR-ABL1 expressing cells became anemic and had to be sacrificed due to illness, however, this was not accompanied by an expansion of human myeloid cells but rather we observed a massive expansion of human T-cells and macrophages/histiocytes. Importantly, control human cells without BCR-ABL1 expression elicited a similar reaction, although with a slight delay of disease induction, suggesting that while BCR-ABL1 contributes to the inflammatory reaction, the presence of normal human hematopoietic cells is detrimental for NSGS mice.

Originalspråkengelska
Artikelnummere0186035
TidskriftPLoS ONE
Volym12
Utgåva10
DOI
StatusPublished - 2017 okt. 1

Ämnesklassifikation (UKÄ)

  • Hematologi
  • Medicinsk genetik

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