In vivo anti-tumor effect of PARP inhibition in IDH1/2 mutant MDS/AML resistant to targeted inhibitors of mutant IDH1/2
Gbyli R, Song Y, Liu W, Gao Y, Biancon G, Chandhok NS, Wang X, Fu X, Patel A, Sundaram R, Tebaldi T, Mamillapalli P, Zeidan AM, Flavell RA, Prebet T, Bindra RS, Halene S. In vivo anti-tumor effect of PARP inhibition in IDH1/2 mutant MDS/AML resistant to targeted inhibitors of mutant IDH1/2. Leukemia 2022, 36: 1313-1323. PMID: 35273342, PMCID: PMC9103411, DOI: 10.1038/s41375-022-01536-x.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaMyelodysplastic syndromeMDS/acute myeloid leukemiaRefractory acute myeloid leukemiaPARP inhibitionVivo anti-tumor effectsAlternate therapeutic optionsSubset of AMLAnti-tumor effectsPre-clinical studiesRibose polymerase inhibitorsSerial transplantation assaysHomologous recombination defectsTherapeutic optionsTreatment optionsOverall engraftmentHigh relapseIDH inhibitionMyeloid leukemiaIsocitrate dehydrogenase 1Small molecule inhibitorsCell frequencyXeno-graftsIDH1/2 mutationsMalignant transformationA highly efficient and faithful MDS patient-derived xenotransplantation model for pre-clinical studies
Song Y, Rongvaux A, Taylor A, Jiang T, Tebaldi T, Balasubramanian K, Bagale A, Terzi YK, Gbyli R, Wang X, Fu X, Gao Y, Zhao J, Podoltsev N, Xu M, Neparidze N, Wong E, Torres R, Bruscia EM, Kluger Y, Manz MG, Flavell RA, Halene S. A highly efficient and faithful MDS patient-derived xenotransplantation model for pre-clinical studies. Nature Communications 2019, 10: 366. PMID: 30664659, PMCID: PMC6341122, DOI: 10.1038/s41467-018-08166-x.Peer-Reviewed Original ResearchConceptsPatient-derived xenograftsMyelodysplastic syndromeXenotransplantation modelDysplastic morphologyImmunodeficient murine hostsPre-clinical studiesMDS stem cellsMDS subtypesComprehensive preclinical studiesPreclinical studiesTherapeutic efficacyMurine hostSerial transplantationDrug mechanismsMDS researchStem cell propagationStem cellsDifferentiation potentialHematopoietic stem cell nicheGenetic complexityNovel avenuesStem cell nicheCell propagationDisease representationsImmunodeficient