2023
Cell circuits between leukemic cells and mesenchymal stem cells block lymphopoiesis by activating lymphotoxin beta receptor signaling
Feng X, Sun R, Lee M, Chen X, Guo S, Geng H, Müschen M, Choi J, Pereira J. Cell circuits between leukemic cells and mesenchymal stem cells block lymphopoiesis by activating lymphotoxin beta receptor signaling. ELife 2023, 12: e83533. PMID: 36912771, PMCID: PMC10042536, DOI: 10.7554/elife.83533.Peer-Reviewed Original ResearchConceptsMesenchymal stem cellsLymphotoxin beta receptorLeukemic cellsBeta receptorsLeukemic cell growthBone marrow microenvironmentStem cellsTransplant recipientsAML cellsMyeloblastic leukemiaMouse modelBone marrowLeukemia growthLymphotoxin α1β2Marrow microenvironmentPharmacological disruptionLymphopoiesisReceptorsHematopoietic outputMolecular mechanismsErythropoiesisDNA damage response pathwayCell growthCellsPhysiological mechanisms
2021
Protein Phosphatase 2A as a Therapeutic Target in Small Cell Lung Cancer
Mirzapoiazova T, Xiao G, Mambetsariev B, Nasser MW, Miaou E, Singhal SS, Srivastava S, Mambetsariev I, Nelson MS, Nam A, Behal A, Arvanitis LD, Atri P, Muschen M, Tissot FLH, Miser J, Kovach JS, Sattler M, Batra SK, Kulkarni P, Salgia R. Protein Phosphatase 2A as a Therapeutic Target in Small Cell Lung Cancer. Molecular Cancer Therapeutics 2021, 20: 1820-1835. PMID: 34253596, PMCID: PMC8722383, DOI: 10.1158/1535-7163.mct-21-0013.Peer-Reviewed Original ResearchConceptsProtein phosphatase 2APhosphatase 2ASerine/threonine phosphataseDNA damage responseRegulation of apoptosisSmall molecule inhibitorsGlycolytic ATP productionThreonine phosphataseTwo-dimensional cultureLB100ATP productionMolecule inhibitorsPP2AThree-dimensional spheroid modelEndothelial cell monolayersGlucose uptakeCell viabilitySCLC cellsTherapeutic targetApoptosisCell monolayersMass spectrometrySpheroid modelTumor spheroidsCells
2019
Metabolic gatekeepers to safeguard against autoimmunity and oncogenic B cell transformation
Müschen M. Metabolic gatekeepers to safeguard against autoimmunity and oncogenic B cell transformation. Nature Reviews Immunology 2019, 19: 337-348. PMID: 30890785, DOI: 10.1038/s41577-019-0154-3.Peer-Reviewed Original ResearchConceptsB cell receptorAutoreactive B cell receptorsLineage-determining transcription factorsMetabolic gatekeeperMitochondrial ATP productionB-cell transformationTranscription factorsEnergy stressPhosphate pathway activityATP productionCell transformationSmall cytoplasmic volumeCell deathPathway activityB cellsEnergy metabolismCell proliferationCytoplasmic volumeCell receptorGlucose uptakeOncogeneB cell proliferationCellsMetabolic demandsAdditional glucose
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 Factors
2013
BACH2 mediates negative selection and p53-dependent tumor suppression at the pre-B cell receptor checkpoint
Swaminathan S, Huang C, Geng H, Chen Z, Harvey R, Kang H, Ng C, Titz B, Hurtz C, Sadiyah MF, Nowak D, Thoennissen GB, Rand V, Graeber TG, Koeffler HP, Carroll WL, Willman CL, Hall AG, Igarashi K, Melnick A, Müschen M. BACH2 mediates negative selection and p53-dependent tumor suppression at the pre-B cell receptor checkpoint. Nature Medicine 2013, 19: 1014-1022. PMID: 23852341, PMCID: PMC3954721, DOI: 10.1038/nm.3247.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBasic-Leucine Zipper Transcription FactorsCell DeathCell DifferentiationCell SurvivalCell Transformation, NeoplasticDNA-Binding ProteinsGene DeletionGene Expression Regulation, LeukemicGreen Fluorescent ProteinsImmunoglobulin mu-ChainsMiceMolecular Sequence DataPAX5 Transcription FactorPre-B Cell ReceptorsPrecursor Cell Lymphoblastic Leukemia-LymphomaPrecursor Cells, B-LymphoidProto-Oncogene Proteins c-bcl-6Proto-Oncogene Proteins c-mycRNA, MessengerSTAT5 Transcription FactorTreatment OutcomeTumor Suppressor Protein p53V(D)J Recombination
2011
BCL6 enables Ph+ acute lymphoblastic leukaemia cells to survive BCR–ABL1 kinase inhibition
Duy C, Hurtz C, Shojaee S, Cerchietti L, Geng H, Swaminathan S, Klemm L, Kweon SM, Nahar R, Braig M, Park E, Kim YM, Hofmann WK, Herzog S, Jumaa H, Koeffler HP, Yu JJ, Heisterkamp N, Graeber TG, Wu H, Ye BH, Melnick A, Müschen M. BCL6 enables Ph+ acute lymphoblastic leukaemia cells to survive BCR–ABL1 kinase inhibition. Nature 2011, 473: 384-388. PMID: 21593872, PMCID: PMC3597744, DOI: 10.1038/nature09883.Peer-Reviewed Original ResearchMeSH KeywordsADP-Ribosylation Factor 1AnimalsCell SurvivalDNA-Binding ProteinsDrug Resistance, NeoplasmFusion Proteins, bcr-ablGene Expression Regulation, NeoplasticHumansMiceMice, Inbred NODMice, SCIDPrecursor Cell Lymphoblastic Leukemia-LymphomaProtein Kinase InhibitorsProto-Oncogene Proteins c-bcl-6Transcription, GeneticTumor Suppressor Protein p53ConceptsTyrosine kinase inhibitorsAcute lymphoblastic leukemia cellsBCR-ABL1 mutationsLymphoblastic leukemia cellsDrug resistanceLeukemia cellsLeukemia-initiating cellsXenograft modelBCR-ABL1Anticancer responseTargeted inhibitionDual inhibitionKinase inhibitorsOncogene withdrawalCancer therapyBCL6Kinase inhibitionLeukemiaInhibitionCellsTherapyMutationsUpregulation
2005
BCR–ABL1 induces aberrant splicing of IKAROS and lineage infidelity in pre-B lymphoblastic leukemia cells
Klein F, Feldhahn N, Herzog S, Sprangers M, Mooster J, Jumaa H, Müschen M. BCR–ABL1 induces aberrant splicing of IKAROS and lineage infidelity in pre-B lymphoblastic leukemia cells. Oncogene 2005, 25: 1118-1124. PMID: 16205638, DOI: 10.1038/sj.onc.1209133.Peer-Reviewed Original ResearchMeSH KeywordsAlternative SplicingAnimalsAntineoplastic AgentsBenzamidesCell Line, TumorCell LineageCell NucleusFusion Proteins, bcr-ablGene Expression ProfilingGene SilencingHumansIkaros Transcription FactorImatinib MesylateMicePiperazinesPrecursor B-Cell Lymphoblastic Leukemia-LymphomaProtein Kinase InhibitorsProtein-Tyrosine KinasesPyrimidinesConceptsLymphoid lineage commitmentLineage commitmentGenome-wide gene expression profilesAberrant splicingLymphoblastic leukemia cellsLeukemia cellsAberrant expressionGene expression profilesNormal B-cell subsetsCell linesPrecursor cell lineLineage identityLineage infidelityTranscription factorsRNA interferenceExpression profilesInducible expressionUndifferentiated phenotypeSplice variantsDefective expressionBCR-ABL1SplicingIk6ExpressionCells
2001
Molecular Single-Cell Analysis of Hodgkin- and Reed-Sternberg Cells Harboring Unmutated Immunoglobulin Variable Region Genes
Müschen M, Küppers R, Spieker T, Bräuninger A, Rajewsky K, Hansmann M. Molecular Single-Cell Analysis of Hodgkin- and Reed-Sternberg Cells Harboring Unmutated Immunoglobulin Variable Region Genes. Laboratory Investigation 2001, 81: 289-295. PMID: 11310822, DOI: 10.1038/labinvest.3780237.Peer-Reviewed Original ResearchConceptsImmunoglobulin variable region genesRegion genesVariable region genesGerminal center B cellsSomatic mutationsFounder cellsGerminal center founder cellsB cellsGenesIntrinsic propensityClonal progenyUnmutated immunoglobulin variable region genesClassical Hodgkin's diseaseAntigen-experienced B cellsCell analysisRS cellsMutationsNaive B cellsReed-Sternberg cellsCellsB-lineageLineagesProgenyClonesApoptosisOct-2 and Bob-1 deficiency in Hodgkin and Reed Sternberg cells.
Re D, Müschen M, Ahmadi T, Wickenhauser C, Staratschek-Jox A, Holtick U, Diehl V, Wolf J. Oct-2 and Bob-1 deficiency in Hodgkin and Reed Sternberg cells. Cancer Research 2001, 61: 2080-4. PMID: 11280769.Peer-Reviewed Original ResearchConceptsImmunoglobulin gene expressionH-RS cellsGene expressionOct-2 transcriptsOct-2 proteinTranscription factor Oct-2Primary H-RS cellsCell linesTranscription machineryBob-1Gene deregulationOctamer siteHodgkin's disease-derived cell linesImmunoglobulin genesNovel mechanismGerminal center B cellsCrippling mutationsClassical Hodgkin's diseaseProtein expressionB cellsTranscriptsExpressionProteinReed-Sternberg cellsCellsEvidence that Hodgkin and Reed-Sternberg cells in Hodgkin disease do not represent cell fusions
Küppers R, Bräuninger A, Müschen M, Distler V, Hansmann M, Rajewsky K. Evidence that Hodgkin and Reed-Sternberg cells in Hodgkin disease do not represent cell fusions. Blood 2001, 97: 818-821. PMID: 11157505, DOI: 10.1182/blood.v97.3.818.Peer-Reviewed Original ResearchConceptsHodgkin's diseaseReed-Sternberg cellsHRS cellsT-cell receptor beta rearrangementsCases of HDClassical Hodgkin's diseaseCoexpression of markersCell fusionNumerical chromosomal abnormalitiesUnusual immunophenotypeT cellsRare caseB cellsBeta rearrangementChromosomal abnormalitiesGermline configurationIgH allelesDifferent hematopoietic lineagesDiseaseHodgkinCell generationCellsTCRbeta allelesHematopoietic lineagesImmunoglobulin genes
2000
Somatic Mutation of the Cd95 Gene in Human B Cells as a Side-Effect of the Germinal Center Reaction
Müschen M, Re D, Jungnickel B, Diehl V, Rajewsky K, Küppers R. Somatic Mutation of the Cd95 Gene in Human B Cells as a Side-Effect of the Germinal Center Reaction. Journal Of Experimental Medicine 2000, 192: 1833-1840. PMID: 11120779, PMCID: PMC2213498, DOI: 10.1084/jem.192.12.1833.Peer-Reviewed Original ResearchConceptsDeath domainCD95 geneSomatic mutationsNegative selectionNon-Ig genesHuman B cellsSomatic hypermutation machineryApoptosis-resistant cellsTumor suppressor geneDD mutationsLast exonHypermutation machinerySuppressor geneApoptosis resistanceGenesB cellsImmunoglobulin genesGerminal center B cellsSomatic hypermutationMutationsCD95 pathwayGC B-cell lymphomasGC B cellsCellsGerminal center reactionDefining CD95 as a tumor suppressor gene
Müschen M, Warskulat U, Beckmann M. Defining CD95 as a tumor suppressor gene. Journal Of Molecular Medicine 2000, 78: 312-325. PMID: 11001528, DOI: 10.1007/s001090000112.Peer-Reviewed Original ResearchConceptsTumor suppressor geneSuppressor geneCD95L expressionReceptor-ligand systemCD95L-mediated apoptosisKey regulatorDe novo expressionMalignant cellsGenesSomatic mutationsCD95 geneLymphocyte homeostasisBystander cellsCD95ApoptosisNatural ligandMalignant progressionNonmalignant counterpartsNovo expressionTumor progressionExpressionCellsTumor cellsGermlineAntitumor immunity