Preclinical evaluation of eltrombopag in a PDX model of myelodysplastic syndromes

  1. Schmitt, Nanni
  2. Jann, Johann-Christoph
  3. Altrock, Eva
  4. Flach, Johanna
  5. Danner, Justine
  6. Uhlig, Stefanie
  7. Streuer, Alexander
  8. Knaflic, Antje
  9. Riabov, Vladimir
  10. Xu, Qingyu
  11. Mehralivand, Arwin ORCID logo
  12. Palme, Iris
  13. Nowak, Verena
  14. Obländer, Julia
  15. Weimer, Nadine
  16. Haselmann, Verena
  17. Jawhar, Ahmed
  18. Darwich, Ali
  19. Weis, Cleo-Aron
  20. Marx, Alexander
  21. Steiner, Laurenz ORCID logo
  22. Jawhar, Mohamad
  23. Metzgeroth, Georgia
  24. Boch, Tobias
  25. Nolte, Florian
  26. Hofmann, Wolf-Karsten
  27. Nowak, Daniel ORCID logo

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1000 Titel
  • Preclinical evaluation of eltrombopag in a PDX model of myelodysplastic syndromes
1000 Autor/in
  1. Schmitt, Nanni |
  2. Jann, Johann-Christoph |
  3. Altrock, Eva |
  4. Flach, Johanna |
  5. Danner, Justine |
  6. Uhlig, Stefanie |
  7. Streuer, Alexander |
  8. Knaflic, Antje |
  9. Riabov, Vladimir |
  10. Xu, Qingyu |
  11. Mehralivand, Arwin |
  12. Palme, Iris |
  13. Nowak, Verena |
  14. Obländer, Julia |
  15. Weimer, Nadine |
  16. Haselmann, Verena |
  17. Jawhar, Ahmed |
  18. Darwich, Ali |
  19. Weis, Cleo-Aron |
  20. Marx, Alexander |
  21. Steiner, Laurenz |
  22. Jawhar, Mohamad |
  23. Metzgeroth, Georgia |
  24. Boch, Tobias |
  25. Nolte, Florian |
  26. Hofmann, Wolf-Karsten |
  27. Nowak, Daniel |
1000 Erscheinungsjahr 2021
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2021-06-25
1000 Erschienen in
1000 Quellenangabe
  • 36(1):236-247
1000 Copyrightjahr
  • 2021
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1038/s41375-021-01327-w |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8727300/ |
1000 Publikationsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • 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.
1000 Sacherschließung
lokal Cancer models
lokal Female [MeSH]
lokal Cell Proliferation [MeSH]
lokal Aged, 80 and over [MeSH]
lokal Myelodysplastic syndrome
lokal Aged [MeSH]
lokal Humans [MeSH]
lokal Pyrazoles/therapeutic use [MeSH]
lokal Middle Aged [MeSH]
lokal Mice, Inbred NOD [MeSH]
lokal Animals [MeSH]
lokal Apoptosis [MeSH]
lokal Mice, SCID [MeSH]
lokal Tumor Cells, Cultured [MeSH]
lokal Mice [MeSH]
lokal Article
lokal Preclinical research
lokal Male [MeSH]
lokal Benzoates/therapeutic use [MeSH]
lokal Xenograft Model Antitumor Assays [MeSH]
lokal Myelodysplastic Syndromes/drug therapy [MeSH]
lokal Prognosis [MeSH]
lokal Hydrazines/therapeutic use [MeSH]
lokal Myelodysplastic Syndromes/pathology [MeSH]
1000 Liste der Beteiligten
  1. https://frl.publisso.de/adhoc/uri/U2NobWl0dCwgTmFubmk=|https://frl.publisso.de/adhoc/uri/SmFubiwgSm9oYW5uLUNocmlzdG9waA==|https://frl.publisso.de/adhoc/uri/QWx0cm9jaywgRXZh|https://frl.publisso.de/adhoc/uri/RmxhY2gsIEpvaGFubmE=|https://frl.publisso.de/adhoc/uri/RGFubmVyLCBKdXN0aW5l|https://frl.publisso.de/adhoc/uri/VWhsaWcsIFN0ZWZhbmll|https://frl.publisso.de/adhoc/uri/U3RyZXVlciwgQWxleGFuZGVy|https://frl.publisso.de/adhoc/uri/S25hZmxpYywgQW50amU=|https://frl.publisso.de/adhoc/uri/UmlhYm92LCBWbGFkaW1pcg==|https://frl.publisso.de/adhoc/uri/WHUsIFFpbmd5dQ==|https://orcid.org/0000-0002-2397-8955|https://frl.publisso.de/adhoc/uri/UGFsbWUsIElyaXM=|https://frl.publisso.de/adhoc/uri/Tm93YWssIFZlcmVuYQ==|https://frl.publisso.de/adhoc/uri/T2Jsw6RuZGVyLCBKdWxpYQ==|https://frl.publisso.de/adhoc/uri/V2VpbWVyLCBOYWRpbmU=|https://frl.publisso.de/adhoc/uri/SGFzZWxtYW5uLCBWZXJlbmE=|https://frl.publisso.de/adhoc/uri/SmF3aGFyLCBBaG1lZA==|https://frl.publisso.de/adhoc/uri/RGFyd2ljaCwgQWxp|https://frl.publisso.de/adhoc/uri/V2VpcywgQ2xlby1Bcm9u|https://frl.publisso.de/adhoc/uri/TWFyeCwgQWxleGFuZGVy|https://orcid.org/0000-0002-4524-037X|https://frl.publisso.de/adhoc/uri/SmF3aGFyLCBNb2hhbWFk|https://frl.publisso.de/adhoc/uri/TWV0emdlcm90aCwgR2VvcmdpYQ==|https://frl.publisso.de/adhoc/uri/Qm9jaCwgVG9iaWFz|https://frl.publisso.de/adhoc/uri/Tm9sdGUsIEZsb3JpYW4=|https://frl.publisso.de/adhoc/uri/SG9mbWFubiwgV29sZi1LYXJzdGVu|https://orcid.org/0000-0001-7130-7921
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1000 Erstellt am 2023-04-27T10:54:33.332+0200
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1000 Zuletzt bearbeitet Fri Oct 20 09:48:56 CEST 2023
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