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

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.

• Author: Maria Askmyr; Sofia Von Palffy; Nils Hansen; Niklas Landberg; Carl Högberg; Marianne Rissler; Helena Ågerstam; Thoas Fioretos
• 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
• Links: http://dx.doi.org/10.1371/journal.pone.0186035
• 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