Publication

Establishing human leukemia xenograft mouse models by implanting human bone marrow-like scaffold-based niches

Antonelli, A., Noort, W. A., Jaques, J., de Boer, B., de Jong-Korlaar, R., Brouwers-Vos, A. Z., Lubbers-Aalders, L., van Velzen, J. F., Bloem, A. C., Yuan, H., de Bruijn, J. D., Ossenkoppele, G. J., Martens, A. C. M., Vellenga, E., Groen, R. W. J. & Schuringa, J. J., 22-Dec-2016, In : Blood. 128, 25, p. 2949-2959 11 p.

Research output: Contribution to journalArticleAcademicpeer-review

Copy link to clipboard

Documents

  • Establishing human leukemia xenograft mouse models by implanting human bone

    Final publisher's version, 2.38 MB, PDF document

    Request copy

DOI

To begin to understand the mechanisms that regulate self-renewal, differentiation, and transformation of human hematopoietic stem cells or to evaluate the efficacy of novel treatment modalities, stem cells need to be studied in their own species-specific microenvironment. By implanting ceramic scaffolds coated with human mesenchymal stromal cells into immune-deficient mice, we were able to mimic the human bone marrow niche. Thus, we have established a human leukemia xenograft mouse model in which a large cohort of patient samples successfully engrafted, which covered all of the important genetic and risk subgroups. We found that by providing a humanized environment, stem cell self-renewal properties were better maintained as determined by serial transplantation assays and genome-wide transcriptome studies, and less clonal drift was observed as determined by exome sequencing. The human leukemia xenograft mouse models that we have established here will serve as an excellent resource for future studies aimed at exploring novel therapeutic approaches.

Original languageEnglish
Pages (from-to)2949-2959
Number of pages11
JournalBlood
Volume128
Issue number25
Publication statusPublished - 22-Dec-2016

    Keywords

  • ACUTE MYELOID-LEUKEMIA, HUMAN HEMATOPOIETIC-CELLS, LONG-TERM EXPANSION, EX-VIVO ASSAYS, STEM-CELLS, XENOTRANSPLANTATION MODEL, SELF-RENEWAL, IMPROVED ENGRAFTMENT, MLL-AF9 LEUKEMIA, NOD/SCID MICE

ID: 40070950