The Molecular Subtype of Adult Acute Lymphoblastic Leukemia Samples Determines the Engraftment Site and Proliferation Kinetics in Patient-Derived Xenograft Models

Richter, Anna and Roolf, Catrin and Sekora, Anett and Knuebel, Gudrun and Krohn, Saskia and Lange, Sandra and Krebs, Vivien and Schneider, Bjoern and Lakner, Johannes and Wittke, Christoph and Kiefel, Christoph and Jeremias, Irmela and Murua Escobar, Hugo and Vollmar, Brigitte and Junghanss, Christian (2022) The Molecular Subtype of Adult Acute Lymphoblastic Leukemia Samples Determines the Engraftment Site and Proliferation Kinetics in Patient-Derived Xenograft Models. Cells, 11 (1). p. 150. ISSN 2073-4409

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Abstract

In acute lymphoblastic leukemia (ALL), conventional cell lines do not recapitulate the clonal diversity and microenvironment. Orthotopic patient-derived xenograft models (PDX) overcome these limitations and mimic the clinical situation, but molecular stability and engraftment patterns have not yet been thoroughly assessed. We herein describe and characterize the PDX generation in NSG mice. In vivo tumor cell proliferation, engraftment and location were monitored by flow cytometry and bioluminescence imaging. Leukemic cells were retransplanted for up to four passages, and comparative analyses of engraftment pattern, cellular morphology and genomic hotspot mutations were conducted. Ninety-four percent of all samples were successfully engrafted, and the xenograft velocity was dependent on the molecular subtype, outcome of the patient and transplantation passage. While BCR::ABL1 blasts were located in the spleen, KMT2A-positive cases had higher frequencies in the bone marrow. Molecular changes appeared in most model systems, with low allele frequency variants lost during primary engraftment. After the initial xenografting, however, the PDX models demonstrated high molecular stability. This protocol for reliable ALL engraftment demonstrates variability in the location and molecular signatures during serial transplantation. Thorough characterization of experimentally used PDX systems is indispensable for the correct analysis and valid data interpretation of preclinical PDX studies.

Item Type: Article
Subjects: Open Asian Library > Biological Science
Depositing User: Unnamed user with email support@openasianlibrary.com
Date Deposited: 07 Jan 2023 09:53
Last Modified: 22 Oct 2024 04:33
URI: http://publications.eprintglobalarchived.com/id/eprint/55

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