EGAGenomicsCancer Genomicshttps://ega-archive.org/studies/EGAS00001005329EGAEGA study EGAS00001005329MDS primary and xenografted samplesEGArestrictedl(2)06430, Mds1-Evi1, HEL2, pafah1b1-b, whole exome, Dmel_CG31829, BOPS, KIAA1546, Jbo, cul3, CUL-3, Cullin 3, dCul3, MDS, Mds, l(2)br34, gft/dCul-3, br34, PRP10, pafah, KCIP-1, Mds1, CG31829, Hsh155, SF3b155, PRPF10, mds, DMcul-3, l35Cd, CUL3, DmelCG42616, cul-3, BG:DS07851.2, guftagu, Cullin3, Exomes, SAP155, dCul-3, LIS1, Evi1, PAFAH, D630039M04Rik, CG11861, platelet-activating factor acetylhydrolase IB subunit alpha, PAFAHA, LIS2, Evi-1, Myelodysplastic Syndromes, MDCR, CG42616, Znfpr1b1, 14-3-3E, Dmel_CG11861, lis2, l(2)35Cd, gft, Prdm3, mdcr, Cul3, myelodysplastic syndrome, susceptibility to.Mds1-Evi1, Safeties, Thrombopoietin receptor, PhrB photolyase activity, Activity, Dmel_CG31829, Laboratory, Heterograft, Blood, Addresses, LACS 1, Jbo, 4-dimethylphenyl)-1, TRANSPL HETEROL, pigmented epithelium, dCul3, Long Term, DSmurf, Facl2, Thrombocytes, diseases, medulla ossea, Mds1, 3, diseases and disorders, Whole Transcriptome, Transcriptome Sequencing, NUP96, Research Activity, epithelium, Laboratory Research, Effect, SF3b155, Priorities, Progression, DMcul-3, human disease, Man (Taxonomy), Dysmyelopoietic Syndrome, reference sample, FACS, preceding., Complete Exome Sequencing, Whole Transcriptome Sequencing, pigmented retina, LIS1, 3'-((2Z)-(1-(3, DNA cyclobutane dipyrimidine photolyase activity, PAFAHA, SUPPRESSOR OF AUXIN RESISTANCE 3, LIS2, Red Marrow, LACS1, MDCR, Xenotransplantations, anucleate thrombocyte, Smurf, lis2, fetal antiepileptic drug syndrome, Acs, Red, Exacerbation, xenotransplant, Homo sapiens disease, mdcr, Research Priority, Thrombopoietin Receptor, Long-Term Effects, myelodysplastic syndrome, CG4943, D-smurf, l(2)06430, PRE, pafah1b1-b, Thrombopoieses, deoxyribonucleic cyclobutane dipyrimidine photolyase activity, Modern, Exome, Blood Platelet, Disease Exacerbation, Thrombocytopoieses, Longterm Effect, Research Priorities, CUL-3, Lack, gft/dCul-3, br34, Antigens, Hematopoetic Myelodysplasia, retinal pigment, agonist, Diseases, dipyrimidine photolyase (photosensitive), 5-dihydro-3-methyl-5-oxo-4H-pyrazol-4-ylidene)hydrazino)-2'-hydroxy-, retinal pigment layer, PRPF10, Heterologous Transplantations, Research and Development, Megakaryocytopoiesis, Xenograft, Complete Transcriptome, l35Cd, Xenotransplantation, SB497115, DmelCG42616, cul-3, DmelCG4943, Transplantation, medulla of bone, susceptibility to, Cullin3, SAP155, Xenografts, Myelodysplastic, CG11861, FAC sorting, platelet-activating factor acetylhydrolase IB subunit alpha, human, experimental procedures, Activities, disease, phr A photolyase activity, DNA-photoreactivating enzyme, fetal AEDS, Syndromes, Znfpr1b1, 14-3-3E, Patient, Myelodysplasias, SB-497 115, Whole Exome Sequencing, blood platelet, Platelet, platelet, Transcriptome Sequencings, Bone, Platelets, humans, HEL2, other disease, human being, (1, Myelodysplasia, experimental, Effects, Complete Exome, dSmurf1, BOPS, Thrombocytopoiesis, MPL Ligand Receptor, cul3, photoreactivating enzyme activity, Transplantations, Cullin 3, l(2)br34, heterologous transplantation, Human, Homo sapiens, pafah, Marrow, thrombocyte, Clinical Progression, Dysmyelopoietic Syndromes, disease or disorder, CG31829, stratum pigmentosa retinae, Yellow, foetal AEDS, Man, Thrombopoietin Receptors, WES, Megakaryocytopoieses, MOS3, CUL3, Complete, methods, deoxyribocyclobutadipyrimidine pyrimidine-lyase activity, Exome Sequencings, Hematopoetic Myelodysplasias, Clinical, PRECOCIOUS, Research, Longterm, 1'-biphenyl)-3-carboxylic acid, experimental section, guftagu, F23A5.3, Heterografts, Evi1, Long-Term, D630039M04Rik, Sequencing, Evi-1, Myelodysplastic Syndromes, non-neoplastic, CD110 Antigens, Whole Exome, d-smurf, Clinical Course, Clients, Whole, Syndrome, disorder, gft, Long-Term Effect, Development and Research, Cul3, Thrombocyte, F23A5_3, Heterologous, Controlled, Acas1, agonista, DDL-701, Myelodysplastic Syndrome, Controlling, Disease, Complete Exome Sequencings, KIAA1546, disorders, medical condition, Dsmurf, Client, MDS, Mds, Hematopoetic, PRP10, dSmurf, Revolade, Exome Sequencing, MODIFIER OF SNC1, Priority, XENOTRANSPL, medulla ossium, Smurf ubiquitin ligase, KCIP-1, Long Term Effects, deoxyribonucleic photolyase activity, Research Activities, SB-497-115, condition, agonists, Hsh155, mds, agoniste, CD110, Yellow Marrow, RPE, Complete Transcriptome Sequencing, photolyase activity, medullary bone, BG:DS07851.2, foetal antiepileptic drug syndrome, HETEROL TRANSPL, patient, dCul-3, PAFAH, enucleate thrombocyte, Longterm Effects, p. pigmentosa retinae, CG42616, Dmel_CG11861, Acas, Modern Man, l(2)35Cd, deoxyribonucleate pyrimidine dimer lyase (photosensitive), Prdm3, Promacta, DysmyelopoieticfalseExome Sequecning of MDS xenografted samplesPre-clinical research of Myelodysplastic Syndromes (MDS) 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 pre-clinical platform to address pending clinical questions by interrogating the efficacy and safety of the thrombopoietin receptor agonist eltrombopag. Our pre-clinical 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.2021-08-18 12:36:00EGAS000010053299606EGAD00001007760EGAC00001002134