2017
Targeting the vulnerability to NAD+ depletion in B-cell acute lymphoblastic leukemia
Takao S, Chien W, Madan V, Lin D, Ding L, Sun Q, Mayakonda A, Sudo M, Xu L, Chen Y, Jiang Y, Gery S, Lill M, Park E, Senapedis W, Baloglu E, Müschen M, Koeffler H. Targeting the vulnerability to NAD+ depletion in B-cell acute lymphoblastic leukemia. Leukemia 2017, 32: 616-625. PMID: 28904384, DOI: 10.1038/leu.2017.281.Peer-Reviewed Original ResearchMeSH KeywordsAcrylamidesAminopyridinesAnimalsAntineoplastic AgentsApoptosisCell Line, TumorCell ProliferationCell SurvivalCytokinesDisease Models, AnimalFemaleHumansMaleMiceNADNicotinamide PhosphoribosyltransferaseP21-Activated KinasesPrecursor B-Cell Lymphoblastic Leukemia-LymphomaSignal TransductionXenograft Model Antitumor AssaysConceptsB-cell acute lymphoblastic leukemiaAcute lymphoblastic leukemiaP21-activated kinase 4Nicotinamide phosphoribosyltransferaseLymphoblastic leukemiaNAMPT inhibitionPatient-derived xenograft murine modelsPrognosis of patientsNicotinamide adenine dinucleotideNovel therapeutic strategiesNicotinic acid supplementationNovel dual inhibitorXenograft murine modelCell growth inhibitionAcid supplementationMurine modelTherapeutic strategiesRate-limiting enzymeCytogenetic abnormalitiesVivo efficacyPatientsNAMPT inhibitorsInhibitory effectDual inhibitorKinase 4
2015
Mechanisms of clonal evolution in childhood acute lymphoblastic leukemia
Swaminathan S, Klemm L, Park E, Papaemmanuil E, Ford A, Kweon SM, Trageser D, Hasselfeld B, Henke N, Mooster J, Geng H, Schwarz K, Kogan SC, Casellas R, Schatz DG, Lieber MR, Greaves MF, Müschen M. Mechanisms of clonal evolution in childhood acute lymphoblastic leukemia. Nature Immunology 2015, 16: 766-774. PMID: 25985233, PMCID: PMC4475638, DOI: 10.1038/ni.3160.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAnimalsAntibody DiversityB-LymphocytesChildChild, PreschoolClonal EvolutionCytidine DeaminaseDNA-Binding ProteinsFemaleFlow CytometryHomeodomain ProteinsHumansImmunoblottingInfantMaleMice, Inbred NODMice, KnockoutMice, SCIDMice, TransgenicMicroscopy, FluorescencePrecursor Cell Lymphoblastic Leukemia-LymphomaPrecursor Cells, B-LymphoidReverse Transcriptase Polymerase Chain ReactionTumor Cells, Cultured
2005
Mimicry of a constitutively active pre–B cell receptor in acute lymphoblastic leukemia cells
Feldhahn N, Klein F, Mooster JL, Hadweh P, Sprangers M, Wartenberg M, Bekhite MM, Hofmann WK, Herzog S, Jumaa H, Rowley JD, Müschen M. Mimicry of a constitutively active pre–B cell receptor in acute lymphoblastic leukemia cells. Journal Of Experimental Medicine 2005, 201: 1837-1852. PMID: 15939795, PMCID: PMC2213268, DOI: 10.1084/jem.20042101.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedCalcium SignalingCell Line, TumorCell SurvivalChildChild, PreschoolFemaleGene Expression Regulation, LeukemicHumansMaleMembrane GlycoproteinsMiddle AgedMolecular MimicryPre-B Cell ReceptorsPrecursor Cell Lymphoblastic Leukemia-LymphomaProtein-Tyrosine KinasesReceptors, Antigen, B-CellConceptsBruton's tyrosine kinaseBCR-ABL1Pre-B cell receptorCell receptorFull‐length Bruton tyrosine kinaseSurvival signalsAcute lymphoblastic leukemia cellsLeukemia cellsBCR-ABL1 kinase activityLymphoblastic leukemia cellsDownstream survival signalsBCR-ABL1 kinaseTyrosine kinaseCell receptor engagementKinase activityBypass selectionSTAT5 phosphorylationSrc homology domain 3BTK activityReceptorsAutonomous Ca2Receptor engagementSimilar extentActivation of PLCgamma1Dependent activation
2004
The BCR-ABL1 Kinase Bypasses Selection for the Expression of a Pre–B Cell Receptor in Pre–B Acute Lymphoblastic Leukemia Cells
Klein F, Feldhahn N, Harder L, Wang H, Wartenberg M, Hofmann WK, Wernet P, Siebert R, Müschen M. The BCR-ABL1 Kinase Bypasses Selection for the Expression of a Pre–B Cell Receptor in Pre–B Acute Lymphoblastic Leukemia Cells. Journal Of Experimental Medicine 2004, 199: 673-685. PMID: 14993251, PMCID: PMC2213306, DOI: 10.1084/jem.20031637.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdolescentAdultAgedBase SequenceCarrier ProteinsChildChild, PreschoolDNA, NeoplasmFemaleFusion Proteins, bcr-ablGene ExpressionGene Rearrangement, B-Lymphocyte, Heavy ChainHumansMaleMembrane GlycoproteinsMiddle AgedPhosphoproteinsPre-B Cell ReceptorsPrecursor B-Cell Lymphoblastic Leukemia-LymphomaProtein-Tyrosine KinasesReceptors, Antigen, B-CellSelection, GeneticConceptsPre-B cell receptorVH region genesWide gene expression profilesPre-B cell receptor signalingFunctional B-cell receptorFunctional pre-B cell receptorCell receptorReceptor engagementAntigen receptor engagementLeukemia cellsCell receptor signalingGene expression profilesRegion genesCell receptor engagementBCR-ABL1 kinase activityB cell receptorImmature B cellsVH gene rearrangementsKinase activityGene expressionExpression profilesAcute lymphoblastic leukemiaReceptor signalingSerial analysisBCR-ABL1
2000
Somatic mutations of the CD95 gene in Hodgkin and Reed-Sternberg cells.
Müschen M, Re D, Bräuninger A, Wolf J, Hansmann M, Diehl V, Küppers R, Rajewsky K. Somatic mutations of the CD95 gene in Hodgkin and Reed-Sternberg cells. Cancer Research 2000, 60: 5640-3. PMID: 11059754.Peer-Reviewed Original ResearchRare Occurrence of Classical Hodgkin's Disease as a T Cell Lymphoma
Müschen M, Rajewsky K, Bräuninger A, Baur A, Oudejans J, Roers A, Hansmann M, Küppers R. Rare Occurrence of Classical Hodgkin's Disease as a T Cell Lymphoma. Journal Of Experimental Medicine 2000, 191: 387-394. PMID: 10637283, PMCID: PMC2195757, DOI: 10.1084/jem.191.2.387.Peer-Reviewed Original ResearchConceptsTCR beta locusMature B cellsGene rearrangementsCell-associated proteinsLight chain gene rearrangementsClassical Hodgkin's diseaseDJ gene rearrangementsIg gene rearrangementsSingle-cell polymerase chain reactionIgH locusCases of cHDClonal progenyBeta gene rearrangementsT cell receptorT cell moleculesLociGermline configurationCell phenotypeCell moleculesLineage derivationB cellsRS cellsCell receptorImmunoglobulin heavyCell markers
1999
Involvement of Soluble CD95 in Churg-Strauss Syndrome
Müschen M, Warskulat U, Perniok A, Even J, Moers C, Kismet B, Temizkan N, Simon D, Schneider M, Häussinger D. Involvement of Soluble CD95 in Churg-Strauss Syndrome. American Journal Of Pathology 1999, 155: 915-925. PMID: 10487849, PMCID: PMC1866905, DOI: 10.1016/s0002-9440(10)65191-7.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedApoptosisCell SurvivalCells, CulturedChurg-Strauss SyndromeClone CellsCulture Media, ConditionedEnzyme-Linked Immunosorbent AssayEosinophilsFas Ligand ProteinFas ReceptorFemaleGenes, T-Cell Receptor betaHumansImmunosuppressive AgentsMaleMembrane GlycoproteinsMiddle AgedMultigene FamilyReceptors, Tumor Necrosis FactorReverse Transcriptase Polymerase Chain ReactionRNA, MessengerT-LymphocytesConceptsChurg-Strauss syndromeSoluble CD95CSS patientsOligoclonal T cell expansionTCR Vbeta gene usageAutoimmune lymphoproliferative disordersVbeta gene usageRole of eosinophilsT cell expansionPeripheral blood lymphocytesT cell clonesSoluble splice variantCD95L-mediated apoptosisCD95 receptor expressionImmunosuppressive therapyClinical improvementCDR3 motifsEffector cellsLymphoproliferative disordersCS patientsBlood lymphocytesReceptor expressionHealthy individualsVbeta genesEosinophilsInvolvement of CD95 (Apo-1/Fas) ligand expressed by rat Kupffer cells in hepatic immunoregulation
Müschen M, Warskulat U, Peters-Regehr T, Bode J, Kubitz R, Häussinger D. Involvement of CD95 (Apo-1/Fas) ligand expressed by rat Kupffer cells in hepatic immunoregulation. Gastroenterology 1999, 116: 666-677. PMID: 10029626, DOI: 10.1016/s0016-5085(99)70189-7.Peer-Reviewed Original ResearchConceptsMessenger RNA levelsKupffer cellsT lymphocytesRat Kupffer cellsRNA levelsInterferon gammaLigand expressionImmune-privileged organQuantitative reverse transcription polymerase chain reactionReverse transcription-polymerase chain reactionReceptor/ligand systemCD95 receptor/ligand systemEnzyme-linked immunosorbent assayCD95 ligand expressionCD95 receptorHepatic immunoregulationPolymerase chain reactionSoluble CD95Inflammatory responseLymphocytesAbstractTextCyclosporin AImmunosorbent assayParenchymal cellsGamma treatment
1998
A critical role for transforming growth factor-beta in donor transfusion-induced allograft tolerance.
Josien R, Douillard P, Guillot C, Müschen M, Anegon I, Chetritt J, Menoret S, Vignes C, Soulillou J, Cuturi M. A critical role for transforming growth factor-beta in donor transfusion-induced allograft tolerance. Journal Of Clinical Investigation 1998, 102: 1920-1926. PMID: 9835616, PMCID: PMC509143, DOI: 10.1172/jci4221.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalBlood TransfusionGraft Enhancement, ImmunologicGraft RejectionGraft SurvivalHeart TransplantationLeukocytesLymphocyte Culture Test, MixedMaleRatsRats, Inbred BUFRats, Inbred LewRNA, MessengerSpleenTissue DonorsTransforming Growth Factor betaTransplantation, HomologousConceptsAllograft toleranceHeart allograft toleranceNonspecific blood transfusionsProlonged graft survivalTh2-related cytokinesTGF-beta1 mRNALater time pointsGraft survivalAllograft rejectionHeart allograftsImmunological mechanismsBlood transfusionRegulatory cellsDonor-SpecificUnmodified recipientsAdult ratsCritical cytokineStrong infiltrationAllograftsTime pointsRecombinant adenovirusCytokinesGraftRatsLeukocytesFas LIGAND, TUMOR NECROSIS FACTOR-α EXPRESSION, AND APOPTOSIS DURING ALLOGRAFT REJECTION AND TOLERANCE
Josien R, Müschen M, Gilbert E, Douillard P, Heslan J, Soulillou J, Cuturi M. Fas LIGAND, TUMOR NECROSIS FACTOR-α EXPRESSION, AND APOPTOSIS DURING ALLOGRAFT REJECTION AND TOLERANCE. Transplantation 1998, 66: 887-893. PMID: 9798699, DOI: 10.1097/00007890-199810150-00013.Peer-Reviewed Original ResearchConceptsAllograft rejectionTNF-alphaDonor-specific blood transfusionApoptotic cellsNecrosis factor α expressionRole of CD95LAcute allograft rejectionDonor-specific transfusionGraft-infiltrating cellsHeterotopic cardiac allograftsCytotoxic T cellsTarget cell lysisTNF-alpha expressionTumor necrosis factorExpression of CD95LCD95/CD95LExpression of FasAcute rejectionCardiac allograftsBlood transfusionIntragraft expressionNecrosis factorT cellsCD95 antigenAllograftsRegulation of CD95 (APO‐1/Fas) receptor and ligand expression by lipopolysaccharide and dexamethasone in parenchymal and nonparenchymal rat liver cells
Müschen M, Warskulat U, Douillard P, Gilbert E, Häussinger D. Regulation of CD95 (APO‐1/Fas) receptor and ligand expression by lipopolysaccharide and dexamethasone in parenchymal and nonparenchymal rat liver cells. Hepatology 1998, 27: 200-208. PMID: 9425938, DOI: 10.1002/hep.510270131.Peer-Reviewed Original ResearchConceptsSinusoidal endothelial cellsNumber of KCsCD95L mRNA levelsKupffer cellsParenchymal cellsMRNA levelsNonparenchymal rat liver cellsNonparenchymal cellsCD95L expressionEffects of lipopolysaccharideMeans of immunocytochemistryLiver Kupffer cellsAddition of supernatantsPresence of lipopolysaccharideLiver cell populationsRat liver Kupffer cellsMessenger RNA levelsCD95 receptorLPS treatmentRat liver cellsThymic lymphocytesCD95 expressionLigand expressionLPS additionPrimary hepatocyte cultures