دورية أكاديمية
The Molecular Subtype of Adult Acute Lymphoblastic Leukemia Samples Determines the Engraftment Site and Proliferation Kinetics in Patient-Derived Xenograft Models
| العنوان: | The Molecular Subtype of Adult Acute Lymphoblastic Leukemia Samples Determines the Engraftment Site and Proliferation Kinetics in Patient-Derived Xenograft Models |
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| المؤلفون: | Anna Richter, Catrin Roolf, Anett Sekora, Gudrun Knuebel, Saskia Krohn, Sandra Lange, Vivien Krebs, Bjoern Schneider, Johannes Lakner, Christoph Wittke, Christoph Kiefel, Irmela Jeremias, Hugo Murua Escobar, Brigitte Vollmar, Christian Junghanss |
| المصدر: | Cells, Vol 11, Iss 1, p 150 (2022) |
| بيانات النشر: | MDPI AG, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Cytology |
| مصطلحات موضوعية: | acute lymphoblastic leukemia, PDX, biobanking, serial transplantation, engraftment site, proliferation kinetics, Cytology, QH573-671 |
| الوصف: | 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. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 11010150 2073-4409 |
| العلاقة: | https://www.mdpi.com/2073-4409/11/1/150Test; https://doaj.org/toc/2073-4409Test |
| DOI: | 10.3390/cells11010150 |
| الوصول الحر: | https://doaj.org/article/21fdd92f54984c47a5294b6e0d5b6d24Test |
| رقم الانضمام: | edsdoj.21fdd92f54984c47a5294b6e0d5b6d24 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 11010150 20734409 |
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| DOI: | 10.3390/cells11010150 |