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Schmitt, Nanni; Jann, Johann-Christoph; Altrock, Eva; Flach, Johanna; Danner, Justine; Uhlig, Stefanie; Streuer, Alexander; Knaflic, Antje; Riabov, Vladimir; Xu, Qingyu; Mehralivand, Arwin; Palme, Iris; Nowak, Verena; Obländer, Julia; Weimer, Nadine; Haselmann, Verena; Jawhar, Ahmed; Darwich, Ali; Weis, Cleo-Aron; Marx, Alexander; Steiner, Laurenz; Jawhar, Mohamad; Metzgeroth, Georgia; Boch, Tobias; [...]

Preclinical evaluation of eltrombopag in a PDX model of myelodysplastic syndromes

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  • Medientyp: E-Artikel
  • Titel: Preclinical evaluation of eltrombopag in a PDX model of myelodysplastic syndromes
  • Beteiligte: Schmitt, Nanni; Jann, Johann-Christoph; Altrock, Eva; Flach, Johanna; Danner, Justine; Uhlig, Stefanie; Streuer, Alexander; Knaflic, Antje; Riabov, Vladimir; Xu, Qingyu; Mehralivand, Arwin; Palme, Iris; Nowak, Verena; Obländer, Julia; Weimer, Nadine; Haselmann, Verena; Jawhar, Ahmed; Darwich, Ali; Weis, Cleo-Aron; Marx, Alexander; Steiner, Laurenz; Jawhar, Mohamad; Metzgeroth, Georgia; Boch, Tobias; [...]
  • Erschienen: Springer Science and Business Media LLC, 2022
  • Erschienen in: Leukemia
  • Sprache: Englisch
  • DOI: 10.1038/s41375-021-01327-w
  • ISSN: 0887-6924; 1476-5551
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>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 <jats:italic>n</jats:italic> = 49 xenografts generated from <jats:italic>n</jats:italic> = 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.</jats:p>