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Thoas Fioretos

Thoas Fioretos

Research team manager

Thoas Fioretos

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

Author

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

Summary, in English

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.

Department/s

  • Translational Genomic and Functional Studies of Leukemia
  • BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation

Publishing year

2017-10-01

Language

English

Publication/Series

PLoS ONE

Volume

12

Issue

10

Document type

Journal article

Publisher

Public Library of Science (PLoS)

Topic

  • Hematology
  • Medical Genetics

Status

Published

Research group

  • Translational Genomic and Functional Studies of Leukemia

ISBN/ISSN/Other

  • ISSN: 1932-6203