2022
SYK and ZAP70 kinases in autoimmunity and lymphoid malignancies
Leveille E, Chan LN, Mirza AS, Kume K, Müschen M. SYK and ZAP70 kinases in autoimmunity and lymphoid malignancies. Cellular Signalling 2022, 94: 110331. PMID: 35398488, DOI: 10.1016/j.cellsig.2022.110331.Peer-Reviewed Original ResearchConceptsChronic lymphocytic leukemiaB-cell malignanciesT cell receptorB cell receptorB-cell chronic lymphocytic leukemiaPathological B-cellsPoor clinical outcomeAcute lymphoblastic leukemiaExpression of SykT lymphocyte developmentClinical outcomesAggressive diseaseActivation of NFATAutoimmune diseasesLymphoblastic leukemiaT lymphocytesLymphocytic leukemiaCell lymphomaLymphoid malignanciesB cellsPI3K-pathwayOncogenic driversMalignancyNegative selectionPremalignant cells
2015
Identification of FOXM1 as a therapeutic target in B-cell lineage acute lymphoblastic leukaemia
Buchner M, Park E, Geng H, Klemm L, Flach J, Passegué E, Schjerven H, Melnick A, Paietta E, Kopanja D, Raychaudhuri P, Müschen M. Identification of FOXM1 as a therapeutic target in B-cell lineage acute lymphoblastic leukaemia. Nature Communications 2015, 6: 6471. PMID: 25753524, PMCID: PMC4366523, DOI: 10.1038/ncomms7471.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsAntineoplastic AgentsB-LymphocytesCell ProliferationCell SurvivalChildClinical Trials as TopicCyclin-Dependent Kinase Inhibitor p16Drug Resistance, NeoplasmForkhead Box Protein M1Forkhead Box Protein O3Forkhead Transcription FactorsGene Expression Regulation, LeukemicHumansMicePeptidesPrecursor Cell Lymphoblastic Leukemia-LymphomaSignal TransductionSurvival AnalysisThiostreptonXenograft Model Antitumor AssaysConceptsAcute lymphoblastic leukemiaLymphoblastic leukemiaTherapeutic targetB-cell lineage acute lymphoblastic leukemiaFOXM1 levelsAggressive clinical coursePre-B cell receptor checkpointNovel therapeutic targetB cell populationsNormal B cell populationsClinical coursePoor outcomeCure rateNormal B cell developmentFOXM1 inhibitionB cell developmentDrug resistanceFoxm1 deletionFOXM1Colony formationPatientsLeukemiaCell survivalPrognosisTranscriptional inactivation
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
2001
Oct-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 cellsCells
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
CD95 ligand expression in dedifferentiated breast cancer
Müschen M, Moers C, Warskulat U, Niederacher D, Betz B, Even J, Lim A, Josien R, Beckmann M, Häussinger D. CD95 ligand expression in dedifferentiated breast cancer. The Journal Of Pathology 1999, 189: 378-386. PMID: 10547600, DOI: 10.1002/(sici)1096-9896(199911)189:3<378::aid-path439>3.0.co;2-d.Peer-Reviewed Original ResearchConceptsReverse transcriptase-polymerase chain reactionBreast cancerCD95 ligand expressionMRNA levelsLigand expressionGrade III breast cancerMammary tissueCD95L mRNA levelsTumor-infiltrating lymphocytesCD95 ligandHigh-grade carcinomaQuantitative reverse transcriptase-polymerase chain reactionBenign mammary tissuesTissue sectionsBreast cancer tissuesNon-malignant mammary tissuesTranscriptase-polymerase chain reactionBreast cancer tissue sectionsBreast cancer sectionsCancer tissue sectionsGrade IGrade IIHistopathological gradingReceptor expressionCancer tissuesInvolvement 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 genesEosinophils