2015
Targeting of Quiescent and Proliferating CML Stem Cells By DNA Repair Inhibitors
Sullivan K, Bolton-Gillespie E, Nieborowska-Skorska M, Cerny-Reiterer S, Valent P, Muschen M, Pomerantz R, Mazin A, Skorski T. Targeting of Quiescent and Proliferating CML Stem Cells By DNA Repair Inhibitors. Blood 2015, 126: 50. DOI: 10.1182/blood.v126.23.50.50.Peer-Reviewed Original ResearchQuiescent leukemia stem cellsLeukemia stem cellsTyrosine kinase inhibitorsChronic myeloid leukemiaCML cellsBCR-ABL1Myeloid leukemiaAnti-leukemia effectSimultaneous targetingCML leukemia stem cellsNew treatment modalitiesPARP1 inhibitorsCML stem cellsNormal counterpartsDouble knockout miceAdditional chromosomal aberrationsTKI-resistant BCRStem cellsBristol-Myers SquibbTKI therapyDisease relapseChronic phaseGood respondersCML patientsTreatment modalities
2014
Gene Expression and Mutation Analysis (GEMA) –Guided Precision Medicine Targeting PARP1 to Induce Synthetic Lethality in DNA-PK –Deficient Quiescent and BRCA-Deficient Proliferating Leukemia Stem and Progenitor Cells
Nieborowska-Skorska M, Sullivan K, Podszywalow-Bartnicka P, Hoser G, Bolton-Gillespie E, Cramer-Morales K, Slupianek A, Zhou C, Cerny-Reiterer S, Stoklosa T, Sykes S, Valent P, Civin C, Muschen M, Minden M, Eppert K, Skorski T. Gene Expression and Mutation Analysis (GEMA) –Guided Precision Medicine Targeting PARP1 to Induce Synthetic Lethality in DNA-PK –Deficient Quiescent and BRCA-Deficient Proliferating Leukemia Stem and Progenitor Cells. Blood 2014, 124: 480. DOI: 10.1182/blood.v124.21.480.480.Peer-Reviewed Original ResearchQuiescent leukemia stem cellsLeukemia progenitor cellsLeukemia stem cellsIndividual patientsPARP1 inhibitorsBCR-ABL1MLL-AF9Progenitor cellsHomologous recombination repairSurvival of miceAML1-ETOAnti-tumor treatmentBone marrow cellsQuiescent cellsMutation analysisCML-CPDisease burdenImmunodeficient miceTumor initiatingLeukemia xenograftsReduced colony formationPatientsPharmacological inhibitionDNA double-strand breaksRepair mechanisms
2013
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
2010
WNT/β-Catenin Signaling in Leukemia
Müschen M. WNT/β-Catenin Signaling in Leukemia. 2010, 129-142. DOI: 10.1007/978-1-4419-8023-6_6.Peer-Reviewed Original ResearchWnt/β-catenin signalingΒ-catenin signalingLeukemia stem cellsLeukemia-initiating cellsStem cellsRelapse of leukemiaMajor clinical problemWnt/β-cateninNovel therapy approachesActive Wnt/β-catenin signalingNormal hematopoiesisTreatment of leukemiaLeukemic cloneClinical problemLeukemia subtypesLeukemiaHematopoietic stem cellsNatural historyDrug resistanceMalignant outgrowthMultiple hematopoietic lineagesProgenitor cellsΒ-cateninTherapy approachesMyeloid progenitorsBCL6 Is Required for the Maintenance of Leukemia-Initiating Cells In Chronic Myeloid Leukemia
Hurtz C, Duy C, Cerchietti L, Chatzi K, Park E, Klemm L, Kim Y, Kahn M, Braig M, Muller M, Hochhaus A, Ye B, Melnick A, Muschen M. BCL6 Is Required for the Maintenance of Leukemia-Initiating Cells In Chronic Myeloid Leukemia. Blood 2010, 116: 202. DOI: 10.1182/blood.v116.21.202.202.Peer-Reviewed Original ResearchDiffuse large B-cell lymphomaNOD/SCID miceChronic myeloid leukemiaHuman CML cellsLeukemia stem cellsTyrosine kinase inhibitorsCML cellsLeukemia-initiating cellsSCID miceMyeloid leukemiaCML patientsBCL6 expressionLeukemia stem cell maintenanceLSK cellsLarge B-cell lymphomaAbsence of Bcl6CML-initiating cellsCML-like leukemiaDistinct side populationStem cellsProtein levelsColony formationGene expression changesB-cell lymphomaLeukemia initiating cellsThe Tumor Suppressor PTEN Is Required to Prevent Cellular Senescence and Cell Cycle Arrest In B Cell Lineage and Chronic Myeloid Leukemia
Shojaee S, Garcia C, Wu H, Muschen M. The Tumor Suppressor PTEN Is Required to Prevent Cellular Senescence and Cell Cycle Arrest In B Cell Lineage and Chronic Myeloid Leukemia. Blood 2010, 116: 513. DOI: 10.1182/blood.v116.21.513.513.Peer-Reviewed Original ResearchB-cell lineage leukemiaCML-like leukemiaChronic myeloid leukemiaB-cell lineageAcute lymphoblastic leukemiaDeletion of PTENLeukemia stem cellsCell cycle arrestT-cell lineageBCR-ABL1Myeloid leukemiaB cell precursorsCellular senescencePI3K/AktCell lineagesLeukemia cell growthEmpty vector controlLeukemia cellsTumor suppressorCML cellsSolid tumorsCycle arrestWestern blotCell precursorsStem cells
2009
Leukemia Stem Cells
Müschen M. Leukemia Stem Cells. 2009, 281-294. DOI: 10.1007/978-90-481-3040-5_13.Peer-Reviewed Original ResearchLeukemia stem cell populationAcute myeloid leukemiaChronic myeloid leukemiaLeukemia stem cellsMyeloid leukemiaLeukemia subtypesCell populationsSelf-renewal capacityStem cellsAcute lymphoblastic leukemia subtypesStem cell populationSubtype of leukemiaRecent dataInitiation of leukemiaLeukemia cell populationsMalignant stem cellsLeukemiaHematopoietic stem cellsExtensive self-renewal capacitySubtypesMulti-lineage potentialCellular origin