Normal ABL1 Is a Tumor Suppressor and Therapeutic Target In BCR-ABL1–positive Leukemias
Dasgupta Y, Koptyra M, Nieborowska-Skorska M, Gillespie E, Stoklosa T, Hoser G, Wasik M, Muschen M, Richardson C, Skorski T. Normal ABL1 Is a Tumor Suppressor and Therapeutic Target In BCR-ABL1–positive Leukemias. Blood 2013, 122: 1466. DOI: 10.1182/blood.v122.21.1466.1466.Peer-Reviewed Original ResearchLeukemia stem cellsCML-CPBCR-ABL1Myeloid differentiationCML blast phaseTumor suppressorEffect of imatinibChronic myeloid leukemiaNovel therapeutic strategiesABL1 kinaseHigher clonogenic activityPositive CML cellsStem cellsBCR-ABL1 kinaseImatinib-treated cellsPotential tumor suppressorChronic phaseCML treatmentLSC compartmentMyeloid leukemiaSCID miceCML CD34Blastic transformationOxidative DNA damageT315I mutationOncogene-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