2017
PON2 Exemplifies a Unique Dependency of B Cell Lineage ALL Cells on Detoxifying Lactonases
Xiao G, Hong C, Geng H, Muschen M. PON2 Exemplifies a Unique Dependency of B Cell Lineage ALL Cells on Detoxifying Lactonases. Blood 2017, 130: 882. DOI: 10.1182/blood.v130.suppl_1.882.882.Peer-Reviewed Original ResearchPatient-derived preB-cell lineageParaoxonase 2BCR-ABL1PON2 expressionB cell developmentB-lineageExpression levelsAdult clinical trialsPON2-deficient miceTime of diagnosisPoor clinical outcomeMRNA levelsBone marrow B cell precursorsSpecific treatment requirementsLactone metabolitesMultiple fetal tissuesG0/G1 phaseB cell precursorsNormal B cellsCell lineagesNormal hematopoietic cellsCell developmentPON2 deficiencyQuantitative RT-PCR
2015
PP2A Is Required for B Cell Survival and Represents a Therapeutic Target in Acute Lymphoblastic Leukemia
Gang X, Geng H, Chan L, Chen Z, Jiang X, Muschen M. PP2A Is Required for B Cell Survival and Represents a Therapeutic Target in Acute Lymphoblastic Leukemia. Blood 2015, 126: 902. DOI: 10.1182/blood.v126.23.902.902.Peer-Reviewed Original ResearchLB-100B cell survivalCell deathH2AX phosphorylationSer/Thr protein phosphatase 2ACell lineagesCell-specific vulnerabilityCell survivalFunction of PP2AEarly B cell developmentProtein phosphatase 2AB-cell lineageCatalytic subunit CGlycolytic fluxAnti-oxidant gene expressionTumor suppressor functionRapid cell deathS6 ribosomal proteinHigh glycolytic fluxB cell developmentImportant tumor suppressorPro-survival roleHigher reactive oxygen species (ROS) levelsCre-mediated deletionPP2A subunits
2014
Divergent Lineage-Specific Functions of PP2A in Chronic Phase CML and Lymphoid Blast Crisis
Xiao G, Geng H, Chan L, Chen Z, Muschen M. Divergent Lineage-Specific Functions of PP2A in Chronic Phase CML and Lymphoid Blast Crisis. Blood 2014, 124: 3128. DOI: 10.1182/blood.v124.21.3128.3128.Peer-Reviewed Original ResearchFunction of PP2ACell lineagesB cell developmentB-cell lineageSer/Thr phosphataseCell developmentPI3K-AktEarly B cell developmentProtein phosphatase 2ALineage-specific functionsNormal B cell developmentChronic phase chronic myeloid leukemiaLineage-specific requirementGlycolytic fluxPre-B cell receptor checkpointMyeloid lineagePhase chronic myeloid leukemiaChronic myeloid leukemiaRegulation of AktS6 ribosomal proteinHigh glycolytic fluxRapid cell deathLymphoid blast crisisImportant tumor suppressorColony formation capabilityBACH2 promotes Lineage-Specific Fate Decisions in BCR-ABL1-Driven Leukemia
Park E, Swaminathan S, Sadiyah M, Igarashi K, Melnick A, Muschen M. BACH2 promotes Lineage-Specific Fate Decisions in BCR-ABL1-Driven Leukemia. Blood 2014, 124: 513. DOI: 10.1182/blood.v124.21.513.513.Peer-Reviewed Original ResearchLymphoid blast crisisFate decisionsB-cell lineageCML-like diseaseCell lineagesTumor suppressorCML cellsBCR-ABL1Transcription factorsTransplant recipientsLineage-specific transcription factorsChronic phaseB-cell-specific transcription factorCell-specific transcription factorsBlast crisisPre-B cell receptor checkpointB-cell lineage leukemiaPrimary human CML cellsRole of Bach2Multi-lineage progenitor cellsEmpty vector controlGene expression analysisSelective proliferative advantagePotent tumor suppressorCML chronic phaseFOXM1 Mediates Drug-Resistance and Represents a Therapeutic Target in Pre-B Acute Lymphoblastic Leukemia
Buchner M, Park E, Klemm L, Geng H, Kopanja D, Raychaudhuri P, Muschen M. FOXM1 Mediates Drug-Resistance and Represents a Therapeutic Target in Pre-B Acute Lymphoblastic Leukemia. Blood 2014, 124: 790. DOI: 10.1182/blood.v124.21.790.790.Peer-Reviewed Original ResearchB cell developmentFOXM1 protein levelsAcute lymphoblastic leukemiaB cell progenitorsB cell precursorsCell developmentFOXO factorsRegulation of FoxM1BCR-ABL1Cell lineagesB-cell lineageBox transcription factor familyCell progenitorsProtein levelsEarly B cell developmentLymphoblastic leukemiaTranscription factor familyCell precursorsGene expression surveyFoxM1 downregulationNormal B cell developmentPre-B cell receptor checkpointFOXM1 expressionTherapeutic targetB cells
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 types
2010
The 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
2007
PAX5-Mediated Lineage Conversion and Expression of AID Accelerates Clonal Evolution and Initiates Darwinian Selection of BCR-ABL1-Mutants in Chronic Myeloid Leukemia.
Klemm L, Feldhahn N, Hoffmann T, Hofmann W, Jumaa H, Muschen M. PAX5-Mediated Lineage Conversion and Expression of AID Accelerates Clonal Evolution and Initiates Darwinian Selection of BCR-ABL1-Mutants in Chronic Myeloid Leukemia. Blood 2007, 110: 1005. DOI: 10.1182/blood.v110.11.1005.1005.Peer-Reviewed Original ResearchLineage conversionCell lineagesDarwinian selectionKinase domainB-cell lineageCell linesSequence analysisEnzyme AIDCML cell linesRetroviral expression constructsTranscription factor Pax5CML linesAID expressionDrug-resistant cellsCell lineage conversionTumor suppressor gene CDKN2ABlast crisis chronic myeloid leukemiaBCR-ABL1 kinase