2018
Autonomous Ca2+ Oscillations Reflect Oncogenic BCR-Signaling in Multiple B-Cell Malignancies and Are Essential for Survival and Proliferation
Kume K, Chen L, Lee J, Muschen M. Autonomous Ca2+ Oscillations Reflect Oncogenic BCR-Signaling in Multiple B-Cell Malignancies and Are Essential for Survival and Proliferation. Blood 2018, 132: 1373. DOI: 10.1182/blood-2018-99-117315.Peer-Reviewed Original ResearchAutonomous Ca2B-cell malignanciesBCR signalingProliferation signalsTime of diagnosisExpression levelsINCA-6B-ALLCell deathMantle cell lymphomaMedian expression levelBCR-ABL1Store-operated Ca2Cell lymphomaHigh expression levelsGenetic experimentsT-cell factorMyeloma cellsPatient-derived xenograft modelsMultiple B-cell malignanciesSurvival signalsFunctional BCRSTIM1/2Relapse-free survivalB-cell lymphoma cellsCooperation between SYK and ZAP70 Kinases As a Driver of Oncogenic BCR-Signaling in B-Cell Malignancies
Sadras T, Cutler J, Aguade-Gorgorio J, Chen Z, Cosgun K, Pandey A, Muschen M. Cooperation between SYK and ZAP70 Kinases As a Driver of Oncogenic BCR-Signaling in B-Cell Malignancies. Blood 2018, 132: 3922. DOI: 10.1182/blood-2018-99-116954.Peer-Reviewed Original ResearchSpleen tyrosine kinaseSH2 domainZAP70 kinaseKinase domainCarboxy-terminal kinase domainLinker regionT cell receptorSurvival signalsBCR signalingTyrosine kinaseChronic lymphocytic leukemiaTandem SH2 domainsProximal signal transductionAmino acid insertB-cell malignanciesBCR-mediated signalsB cellsAlternative splice variantsNegative B cell selectionDifferential interactomeProteomic approachInterdomain BZAP70 proteinBCR componentsSignal transduction
2008
Pre-B Cell Receptor Signaling Prevents Leukemic Transformation by BCR-ABL1
Trageser D, Duy C, Klemm L, Gruber T, Nahar R, Park E, Kim Y, Groffen J, Heisterkamp N, Hofmann W, Martinelli G, Williams R, Jumaa H, Muschen M. Pre-B Cell Receptor Signaling Prevents Leukemic Transformation by BCR-ABL1. Blood 2008, 112: 15. DOI: 10.1182/blood.v112.11.15.15.Peer-Reviewed Original ResearchFunctional pre-B cell receptorAcute lymphoblastic leukemiaBCR-ABL1Pre-B cell receptorCell receptorBone marrowPre-B cell receptor functionTransgenic miceLeukemic transformationLeukemic growthNOD/SCID miceWeight lossLeukemia cellsReceptor selectionTransgenic mouse modelSignificant weight lossPre-B cell receptor signalingBCR-ABL1 expressionSigns of diseaseSurvival signalsEarly B cell developmentLeukemic infiltrationSplenic enlargementCell receptor signalingPeripheral blood
2007
Pre-B Cell Receptor Signaling Prevents Leukemic Transformation by BCR-ABL1.
Trageser D, Klemm L, Herzog S, Kim Y, Duy C, Hofmann W, Groffen J, Heisterkamp N, Jumaa H, Muschen M. Pre-B Cell Receptor Signaling Prevents Leukemic Transformation by BCR-ABL1. Blood 2007, 110: 2795. DOI: 10.1182/blood.v110.11.2795.2795.Peer-Reviewed Original ResearchPre-B cell receptorFunctional pre-B cell receptorImmunoglobulin heavy chain locusAcute lymphoblastic leukemiaBCR-ABL1Cell receptorSurvival signalsPre-B cell receptor signalingReceptor selectionEarly B cell developmentBone marrowPre-B cell receptor functionTransgenic miceLeukemic transformationCell receptor signalingRapid cell deathB cell developmentHuman BCR-ABL1Potent tumor suppressorHeavy chain locusPre B cellsSingle-cell PCRTransgenic mouse modelCell receptor functionB cell precursors
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