2023
Separation of B- and T-Cell-Specific Signaling Molecules Prevents Oncogenic Transformation in Lymphoid Malignancies
Ketzer F, Klemm L, Robinson M, Loucks C, Arce D, Cosgun K, Kothari S, Müschen M. Separation of B- and T-Cell-Specific Signaling Molecules Prevents Oncogenic Transformation in Lymphoid Malignancies. Blood 2023, 142: 1396. DOI: 10.1182/blood-2023-189221.Peer-Reviewed Original ResearchKinase ZAP70Transcriptional regulationTranscription factorsKinase SykDownstream activationT-cell signaling proteinsCRISPR/Cas9-mediated knockoutComparative proteomic analysisNegative selectionFunction of proteinsWild-type cellsCas9-mediated knockoutCo-expressed proteinsPre-malignant cellsT cell linesCellular fitnessTranscription machinerySLP-76Signaling proteinsMalignant transformationSignal transductionAberrant transcriptionProteomic analysisChIP-qPCRNovel key mechanism
2018
Divergent Evolutionary Trajectories of Erk- and Stat5-Activating Lesions in Acute Lymphoblastic Leukemia
Chan L, Shojaee S, Hurtz C, Auer F, Chen Z, Cosgun K, Geng H, Sadras T, White D, Muschen M. Divergent Evolutionary Trajectories of Erk- and Stat5-Activating Lesions in Acute Lymphoblastic Leukemia. Blood 2018, 132: 568. DOI: 10.1182/blood-2018-99-115536.Peer-Reviewed Original ResearchEvolutionary trajectoriesColony formation abilityCompetitive fitnessCommitment stepPre-B cell receptorDivergent evolutionary trajectoriesUpstream kinase MEKNormal B cell developmentOncogenic signal transductionInducible ablationActivation of STAT5B cell developmentEmpty vector controlActivation of ERKCentral oncogenic driverB-cell transformationImmature B cellsSignal transductionFormation abilityKinase MEKPhosphorylation of ERKGrowth factor receptorPatient-derived preAlternative pathwayERK activityCooperation 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
2006
The SRC family kinase LYN redirects B cell receptor signaling in human SLP65-deficient B cell lymphoma cells
Sprangers M, Feldhahn N, Herzog S, Hansmann M, Reppel M, Hescheler J, Jumaa H, Siebert R, Müschen M. The SRC family kinase LYN redirects B cell receptor signaling in human SLP65-deficient B cell lymphoma cells. Oncogene 2006, 25: 5056-5062. PMID: 16568084, DOI: 10.1038/sj.onc.1209510.Peer-Reviewed Original ResearchConceptsB-cell lymphoma cellsB cell receptor engagementCell lymphoma cellsSrc kinase LynCell receptor engagementB cell receptorKinase LynReceptor-induced Ca2Lymphoma cellsCell receptorReceptor engagementB-cell receptor signal transductionSrc family kinase LynB-cell-derived lymphomasSrc kinase activityReceptor signal transductionAcute lymphoblastic leukemiaSrc kinase activationProliferation-related moleculesB-cell lymphoma casesReceptor-dependent Ca2Normal B cellsActivation of survivalSignal transductionRNA interference
2004
The BCR-ABL1 Kinase Interferes with Pre-B Cell Receptor Signal Transduction in B Cell Precursor Leukemia Cells.
Klein F, Feldhahn N, Wernet P, Müschen M. The BCR-ABL1 Kinase Interferes with Pre-B Cell Receptor Signal Transduction in B Cell Precursor Leukemia Cells. Blood 2004, 104: 1894. DOI: 10.1182/blood.v104.11.1894.1894.Peer-Reviewed Original ResearchPre-B cell receptorReceptor signal transductionSignal transductionVH gene rearrangementsBCR-ABL1 kinase activityPre-B cell receptor (pre-BCR) signalsKinase activityGenome-wide gene expressionReceptor engagementSignal transduction cascadeLeukemia cellsCell receptorAntigen receptor engagementReceptor-dependent signal transductionNovel target geneCell receptor signalingBCR-ABL1 kinaseApoptotic cell deathCell receptor signalsGene rearrangementsCell receptor engagementBCR-ABL1B cell receptorImmature B cellsTarget genes