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
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
2012
BCL6 Interacting Corepressor (BCOR) Functions As Lineage-Specific Tumor Suppressor in B Lymphoid and Myeloid Leukemia
Shojaee S, Geng H, Gearhart M, Bardwell V, Muschen M. BCL6 Interacting Corepressor (BCOR) Functions As Lineage-Specific Tumor Suppressor in B Lymphoid and Myeloid Leukemia. Blood 2012, 120: 1301. DOI: 10.1182/blood.v120.21.1301.1301.Peer-Reviewed Original ResearchB-cell lineageMyeloid leukemiaLeukemia cellsBCR-ABL1B-lymphoidTKI sensitivityBCOR overexpressionLoxP-flanked STOP cassetteCML-like leukemiaProgenitor cellsTumor suppressorBone marrow hematopoietic stemAcute myeloid leukemiaBone marrow progenitor cellsCell lineagesMarrow progenitor cellsTumor suppressor roleMyelodysplastic syndromeMale miceTKI resistanceCML cellsLoxP-flanked allelesFatal diseaseTumor growthLeukemia typesLineage-Specific Functions of LKB1 in CML and B Lymphoid Blast Crisis
Chan L, Geng H, Muschen M. Lineage-Specific Functions of LKB1 in CML and B Lymphoid Blast Crisis. Blood 2012, 120: 34. DOI: 10.1182/blood.v120.21.34.34.Peer-Reviewed Original ResearchBCR-ABL1LBC cellsImatinib treatmentInactivation of AMPKBlast crisisCancer cellsSolid tumorsB-lymphoid blast crisisHematopoietic stem cellsLKB1 deletionTumor suppressorInitial proliferative burstProgenitor cellsPoor clinical outcomeBone marrow hematopoietic stemAerobic glycolysisB-cell precursor cellsLymphoid blast crisisCML blast crisisTamoxifen-inducible CrePhospho-p70 S6 kinaseHematopoietic stemClinical outcomesRole of LKB1Lymphoblastic leukemia
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 progenitors