Oncogene-Induced DNA Repair Defects Promote PARP1-Mediated “Dual Synthetic Lethality” To Eradicate Quiescent and Proliferating Leukemia Stem and Progenitor Cells
Nieborowska-Skorska M, Slupianek A, Hoser G, Bolton-Gillespie E, Tulin A, Cerny-Reiterer S, Valent P, Muschen M, Sykes S, Skorski T. Oncogene-Induced DNA Repair Defects Promote PARP1-Mediated “Dual Synthetic Lethality” To Eradicate Quiescent and Proliferating Leukemia Stem and Progenitor Cells. Blood 2013, 122: 810. DOI: 10.1182/blood.v122.21.810.810.Peer-Reviewed Original ResearchQuiescent leukemia stem cellsLeukemia progenitor cellsLeukemia stem cellsImatinib-naïveLeukemia cellsAML1-ETOBCR-ABL1PARP1 inhibitorsProgenitor cellsNormal cellsAnti-leukemia effectPositive AML cellsBCR-ABL1 T315I mutationInhibited colony formationAnti-proliferative effectsPARP inhibitor olaparibStem cellsModest inhibitory effectInhibition of PARPPeripheral bloodDisease burdenBone marrow nicheClinical trialsAML cellsT315I mutation