2022
ACTR5 controls CDKN2A and tumor progression in an INO80-independent manner
Xu X, Chan A, Li M, Liu Q, Mattson N, Pokharel S, Chang W, Yuan Y, Wang J, Moore R, Pirrotte P, Wu J, Su R, Müschen M, Rosen S, Chen J, Yang L, Chen C. ACTR5 controls CDKN2A and tumor progression in an INO80-independent manner. Science Advances 2022, 8: eadc8911. PMID: 36563143, PMCID: PMC9788768, DOI: 10.1126/sciadv.adc8911.Peer-Reviewed Original ResearchCell cycle signalingCRISPR interference screenCell cycle machineryHallmark of tumorigenesisINO80 chromatinInterference screenEpigenetic regulatorsTumor progressionEpigenetic mechanismsCycle machineryEpigenetic dysregulationComplex membersTumor suppressorCell cycleCRISPR geneHCC tumor growthIes6CDKN2A expressionPharmacological inhibitionSignalingMultiple cancersHCC proliferationNovel opportunitiesTumor growthDynamic interplay
2018
Pre-BCR Surrogate Light Chain Components VPREB1 and IGLL1 Function As Pre-BCR-Independent Tumor Suppressors in Acute Lymphoblastic Leukemia
Cosgun K, Hendriks R, Dickins R, Heisterkamp N, Muschen M. Pre-BCR Surrogate Light Chain Components VPREB1 and IGLL1 Function As Pre-BCR-Independent Tumor Suppressors in Acute Lymphoblastic Leukemia. Blood 2018, 132: 570. DOI: 10.1182/blood-2018-99-115522.Peer-Reviewed Original ResearchBCR-ABL1Transgenic miceSurrogate light chainTime of diagnosisTime of relapseDouble transgenic miceExerts tumor-suppressive effectsAcute lymphoblastic leukemiaB cell defectsDay of birthBCR-ABL1 tyrosine kinaseHigh surface levelsTumor-suppressive effectsPre-BCR expressionColony formation abilityPhosphorylation of BtkTumor suppressorBCR-ABL1 oncogeneEarly B cell developmentTumor suppressive functionLymphoblastic leukemiaCell cycle arrestFrequent lesionsSecondary lesionsSuppressive functionB-Cell-Specific Diversion of Glucose Carbon Utilization Reveals a Unique Vulnerability in B Cell Malignancies
Xiao G, Chan LN, Klemm L, Braas D, Chen Z, Geng H, Zhang QC, Aghajanirefah A, Cosgun KN, Sadras T, Lee J, Mirzapoiazova T, Salgia R, Ernst T, Hochhaus A, Jumaa H, Jiang X, Weinstock DM, Graeber TG, Müschen M. B-Cell-Specific Diversion of Glucose Carbon Utilization Reveals a Unique Vulnerability in B Cell Malignancies. Cell 2018, 173: 470-484.e18. PMID: 29551267, PMCID: PMC6284818, DOI: 10.1016/j.cell.2018.02.048.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsB-LymphocytesCarbonCell Line, TumorCell SurvivalGlucoseGlucosephosphate DehydrogenaseGlycolysisHumansIkaros Transcription FactorMiceMice, Inbred C57BLMice, Inbred NODOxidative StressPAX5 Transcription FactorPentose Phosphate PathwayPrecursor Cell Lymphoblastic Leukemia-LymphomaProtein Phosphatase 2Proto-Oncogene Proteins c-bcl-2Transcription, GeneticConceptsPentose phosphate pathwayCarbon utilizationSerine/threonine protein phosphatase 2AB-cell transcription factor PAX5Transcription factor Pax5Favor of glycolysisSmall molecule inhibitionPhosphatase 2ATranscriptional repressionRedox homeostasisOncogenic transformationTumor suppressorMolecule inhibitionPP2AGenetic studiesPhosphate pathwayB cell activationEssential roleB-cell malignanciesCell malignanciesB cellsAntioxidant protectionOxidative stressB-cell tumorsCell activation
2017
Metabolic gatekeeper function of B-lymphoid transcription factors
Chan LN, Chen Z, Braas D, Lee JW, Xiao G, Geng H, Cosgun KN, Hurtz C, Shojaee S, Cazzaniga V, Schjerven H, Ernst T, Hochhaus A, Kornblau SM, Konopleva M, Pufall MA, Cazzaniga G, Liu GJ, Milne TA, Koeffler HP, Ross TS, Sánchez-García I, Borkhardt A, Yamamoto KR, Dickins RA, Graeber TG, Müschen M. Metabolic gatekeeper function of B-lymphoid transcription factors. Nature 2017, 542: 479-483. PMID: 28192788, PMCID: PMC5621518, DOI: 10.1038/nature21076.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAMP-Activated Protein Kinase KinasesAMP-Activated Protein KinasesAnimalsB-LymphocytesCarcinogenesisCarrier ProteinsCell DeathChromatin ImmunoprecipitationCitric Acid CycleDisease Models, AnimalEnergy MetabolismFemaleGene Expression Regulation, NeoplasticGlucocorticoidsGlucoseHumansIkaros Transcription FactorMiceMice, TransgenicPAX5 Transcription FactorPrecursor B-Cell Lymphoblastic Leukemia-LymphomaProtein Serine-Threonine KinasesPyruvic AcidReceptor, Cannabinoid, CB2Receptors, GlucocorticoidSequence Analysis, RNATranscription FactorsGenetic analysis of Ikaros target genes and tumor suppressor function in BCR-ABL1+ pre–B ALL
Schjerven H, Ayongaba EF, Aghajanirefah A, McLaughlin J, Cheng D, Geng H, Boyd JR, Eggesbø LM, Lindeman I, Heath JL, Park E, Witte ON, Smale ST, Frietze S, Müschen M. Genetic analysis of Ikaros target genes and tumor suppressor function in BCR-ABL1+ pre–B ALL. Journal Of Experimental Medicine 2017, 214: 793-814. PMID: 28190001, PMCID: PMC5339667, DOI: 10.1084/jem.20160049.Peer-Reviewed Original ResearchConceptsTumor suppressor functionHuman BCR-ABL1Target genesSuppressor functionDevelopmental stage-specific expressionGenome-wide chromatinStage-specific expressionWild-type IkarosTumor suppressor geneChromatin compactionIkaros functionGene pathwaysMultiple genesExpression analysisGenetic analysisInducible expressionTumor suppressorGenetic depletionCell surface markers CD34Suppressor geneGenesIkarosBCR-ABL1Cell acute lymphoblastic leukemiaLeukemic growth
2016
Analysis of Ikaros tumor suppressor function in BCR-ABL1+ pre-B ALL reveals conserved target genes and biological pathways
Schjerven H, Ayongaba E, McLaughlin J, Cheng D, Eggesbø L, Lindeman I, Park E, Witte O, Smale S, Frietze S, Muschen M. Analysis of Ikaros tumor suppressor function in BCR-ABL1+ pre-B ALL reveals conserved target genes and biological pathways. The Journal Of Immunology 2016, 196: 122.6-122.6. DOI: 10.4049/jimmunol.196.supp.122.6.Peer-Reviewed Original ResearchTumor suppressor functionTarget genesDevelopmental stage-specific expressionSuppressor functionB cell developmentStem cell signatureZinc fingerHematopoietic developmentIkaros DNAIkaros functionEarly hematopoietic progenitor cellsHematopoietic progenitor cellsRNA sequencingReceptor c-kitMultiple genesBiological functionsInducible expressionTumor suppressionTumor suppressorBiological pathwaysSpecific expressionAdhesion pathwayCritical regulatorIkarosGenes
2015
Ikaros tumor suppressor function in pre-B ALL: potential role of Ikaros target gene Ctnnd1 (IRM10P.621)
Schjerven H, Eggesbo L, Lindeman I, Muschen M. Ikaros tumor suppressor function in pre-B ALL: potential role of Ikaros target gene Ctnnd1 (IRM10P.621). The Journal Of Immunology 2015, 194: 131.19-131.19. DOI: 10.4049/jimmunol.194.supp.131.19.Peer-Reviewed Original ResearchTumor suppressor functionTarget genesSuppressor functionDNA-binding zinc fingersTumor suppressorGenome-wide expression analysisHuman preZinc finger transcription factorFinger transcription factorIndirect target genesDownstream target genesB cell developmentImportant tumor suppressorRole of IkarosProper hematopoiesisZinc fingerChIP-seqRNA-seqTranscription factorsPatient-derived preExpression analysisPotential roleIkarosGenesIkaros expression
2014
BACH2 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 phase
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 mutation
2012
Integrative Analysis of Ikaros-Dependent Changes of Transcriptional Regulation and Tyrosine Phosphorylation Events in Ph+ ALL
Geng H, Nahar R, Ramezani-Rad P, Chen Z, Tyner J, Chang B, Titz B, Buchner M, Hurtz C, Graeber T, Druker B, Paietta E, Melnick A, Willman C, Carroll W, Muschen M. Integrative Analysis of Ikaros-Dependent Changes of Transcriptional Regulation and Tyrosine Phosphorylation Events in Ph+ ALL. Blood 2012, 120: 528. DOI: 10.1182/blood.v120.21.528.528.Peer-Reviewed Original ResearchGene expression changesTyrosine phosphorylation eventsExpression changesTarget genesPhosphorylation eventsIkaros functionTyrosine phosphorylationClinical trial fundingTumor suppressorAbility of IkarosDependent survival signalsTyrosine kinase LckClinical trialsSet of genesBCL6 target genesComprehensive gene expression analysisChIP-seq dataIkaros transcription factorGene expression analysisRole of IkarosGene expression microarraysTrial fundingBristol-Myers SquibbClinical outcomesFurther biochemistryBCL6 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
2011
Mechanisms of Ikaros-Mediated Tumor Suppression
Nahar R, Ramezani-Rad P, Dovat S, Buchner M, Graeber T, Muschen M. Mechanisms of Ikaros-Mediated Tumor Suppression. Blood 2011, 118: 408. DOI: 10.1182/blood.v118.21.408.408.Peer-Reviewed Original ResearchPre-B cell receptor signalingPre-B cell receptorCell receptor signalingAbility of IkarosGene expression changesTumor suppressor pathwayTumor suppressionTumor suppressorDephosphorylation eventsReceptor signalingGenetic evidenceSuppressor pathwayAdapter moleculeExpression changesCritical phosphorylation eventsCommon gene expression changesCell receptorTumor-suppressive transcription factorCell cycle exitSimilar gene expression changesComprehensive gene expression analysisARF/p53 pathwayLeukemia cellsBCR-ABL1 kinaseCell cycle progression
2010
IKAROS and BCL6 Limit Pre-B Cell Expansion and Prevent Leukemogenesis Downstream of the Pre-B Cell Receptor
Nahar R, Ramezani-Rad P, Duy C, Dovat S, Ye B, Melnick A, Muschen M. IKAROS and BCL6 Limit Pre-B Cell Expansion and Prevent Leukemogenesis Downstream of the Pre-B Cell Receptor. Blood 2010, 116: 146. DOI: 10.1182/blood.v116.21.146.146.Peer-Reviewed Original ResearchPre-B cell receptorCell cycle arrestCell cycle progressionTumor suppressorCycle arrestTumor suppressionIkaros functionCycle progressionNegative cell cycle regulationSignaling leadsDephosphorylation of STAT5Cell receptorIkaros expressionBCL6 transcriptional repressorGenome-wide ChIPPre-B cell expansionCell cycle regulationSubsequent cell cycle arrestCentral mediatorOverexpression of MYCProliferation downstreamTranscriptional repressionGenetic experimentsTranscriptional repressorTranscriptional activationThe 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