Please use this identifier to cite or link to this item: doi:10.22028/D291-30113
Title: Optimized Xenograft Protocol for Chronic Lymphocytic Leukemia Results in High Engraftment Efficiency for All CLL Subgroups
Author(s): Decker, Sarah
Zwick, Anabel
Khaja Saleem, Shifa
Kissel, Sandra
Rettig, Andres
Aumann, Konrad
Dierks, Christine
Language: English
Title: International Journal of Molecular Sciences
Volume: 20
Issue: 24
Publisher/Platform: MDPI
Year of Publication: 2019
Free key words: CLL
DDC notations: 610 Medicine and health
Publikation type: Journal Article
Abstract: Preclinical drug development for human chronic lymphocytic leukemia (CLL) requires robust xenograft models recapitulating the entire spectrum of the disease, including all prognostic subgroups. Current CLL xenograft models are hampered by inefficient engraftment of good prognostic CLLs, overgrowth with co-transplanted T cells, and the need for allogeneic humanization or irradiation. Therefore, we aimed to establish an effective and reproducible xenograft protocol which allows engraftment of all CLL subtypes without the need of humanization or irradiation. Unmanipulated NOD.Cg-PrkdcscidIl2rgtm1Sug/JicTac (NOG) mice in contrast to C.Cg-Rag2tm1Fwa-/- Il2rgtm1Sug/JicTac (BRG) mice allowed engraftment of all tested CLL subgroups with 100% success rate, if CLL cells were fresh, injected simultaneously intra-peritoneally and intravenously, and co-transferred with low fractions of autologous T cells (2%–4%). CLL transplanted NOG mice (24 different patients) developed CLL pseudofollicles in the spleen, which increased over 4–6 weeks, and were then limited by the expanding autologous T cells. Ibrutinib treatment studies were performed to validate our model, and recapitulated treatment responses seen in patients. In conclusion, we developed an easy-to-use CLL xenograft protocol which allows reliable engraftment for all CLL subgroups without humanization or irradiation of mice. This protocol can be widely used to study CLL biology and to explore novel drug candidates.
DOI of the first publication: 10.3390/ijms20246277
Link to this record: urn:nbn:de:bsz:291--ds-301134
ISSN: 1422-0067
Date of registration: 9-Dec-2020
Description of the related object: Supplementary Materials
Related object:
Faculty: M - Medizinische Fakultät
Department: M - Infektionsmedizin
Professorship: M - Keiner Professur zugeordnet
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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