Preclinical evaluation of eltrombopag in a PDX model of myelodysplastic syndromes
Preclinical research of myelodysplastic syndromes (MDSs) is hampered by a lack of feasible disease models. Previously, we have established a robust patient-derived xenograft (PDX) model for MDS. Here we demonstrate for the first time that this model is applicable as a preclinical platform to address...
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2022
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| In: |
Leukemia
Year: 2022, Volume: 36, Issue: 1, Pages: 236-247 |
| ISSN: | 1476-5551 |
| DOI: | 10.1038/s41375-021-01327-w |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41375-021-01327-w Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41375-021-01327-w 
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| Author Notes: | Nanni Schmitt, Johann-Christoph Jann, Eva Altrock, Johanna Flach, Justine Danner, Stefanie Uhlig, Alexander Streuer, Antje Knaflic, Vladimir Riabov, Qingyu Xu, Arwin Mehralivand, Iris Palme, Verena Nowak, Julia Obländer, Nadine Weimer, Verena Haselmann, Ahmed Jawhar, Ali Darwich, Cleo-Aron Weis, Alexander Marx, Laurenz Steiner, Mohamad Jawhar, Georgia Metzgeroth, Tobias Boch, Florian Nolte, Wolf-Karsten Hofmann, Daniel Nowak |
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| 245 | 1 | 0 | |a Preclinical evaluation of eltrombopag in a PDX model of myelodysplastic syndromes |c Nanni Schmitt, Johann-Christoph Jann, Eva Altrock, Johanna Flach, Justine Danner, Stefanie Uhlig, Alexander Streuer, Antje Knaflic, Vladimir Riabov, Qingyu Xu, Arwin Mehralivand, Iris Palme, Verena Nowak, Julia Obländer, Nadine Weimer, Verena Haselmann, Ahmed Jawhar, Ali Darwich, Cleo-Aron Weis, Alexander Marx, Laurenz Steiner, Mohamad Jawhar, Georgia Metzgeroth, Tobias Boch, Florian Nolte, Wolf-Karsten Hofmann, Daniel Nowak |
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| 520 | |a Preclinical research of myelodysplastic syndromes (MDSs) is hampered by a lack of feasible disease models. Previously, we have established a robust patient-derived xenograft (PDX) model for MDS. Here we demonstrate for the first time that this model is applicable as a preclinical platform to address pending clinical questions by interrogating the efficacy and safety of the thrombopoietin receptor agonist eltrombopag. Our preclinical study included n = 49 xenografts generated from n = 9 MDS patient samples. Substance efficacy was evidenced by FACS-based human platelet quantification and clonal bone marrow evolution was reconstructed by serial whole-exome sequencing of the PDX samples. In contrast to clinical trials in humans, this experimental setup allowed vehicle- and replicate-controlled analyses on a patient-individual level deciphering substance-specific effects from natural disease progression. We found that eltrombopag effectively stimulated thrombopoiesis in MDS PDX without adversely affecting the patients’ clonal composition. In conclusion, our MDS PDX model is a useful tool for testing new therapeutic concepts in MDS preceding clinical trials. | ||
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