2023
CD25 recruits inhibitory phosphatases for feedback control of B-cell receptor signaling
Sun R, Lee J, Robinson M, Kume K, Cosgun K, Chan L, Leveille E, Geng H, Vykunta V, Shy B, Marson A, Meffre E, Müschen M. CD25 recruits inhibitory phosphatases for feedback control of B-cell receptor signaling. The Journal Of Immunology 2023, 210: 154.23-154.23. DOI: 10.4049/jimmunol.210.supp.154.23.Peer-Reviewed Original ResearchAntigen-experienced B cellsB cellsEarly B cell developmentGerminal centersB cell developmentSpontaneous germinal centersCD25 surface expressionAutoreactive B cellsRole of CD25B cell toleranceB-cell receptor signalingB-cell leukemiaB cell receptorAutoantibody productionCD25Cell toleranceGenetic ablationReceptor signalingBCR signalingOncogenic signalingInhibitorySuccessful initiationSignalingNegative selectionAutoimmunity
2021
Identification of a Conserved Intracellular Loop (CIL) Structure That Scaffolds PIP3 to Amplify Oncogenic Signaling during Malignant B-Cell Transformation
Lee J, Robinson M, Ma N, Sadras T, Cosgun K, Chan L, Kume K, Thomas-Tikhonenko A, Weinstock D, Diamond M, Vaidehi N, Müschen M. Identification of a Conserved Intracellular Loop (CIL) Structure That Scaffolds PIP3 to Amplify Oncogenic Signaling during Malignant B-Cell Transformation. Blood 2021, 138: 868. DOI: 10.1182/blood-2021-149646.Peer-Reviewed Original ResearchLipid raftsB cell receptorB cell activationB cell activation signalsConstitutive membrane localizationMalignant B-cell transformationPleckstrin homology domainCell membrane lipid compositionMembrane lipid compositionNormal B-cell activationEndosomal proteinCell membrane lipidsBasic lysine residueHomology domainPH domainMembrane localizationB-cell transformationProteomic analysisEndosomal membranesPIP3PIP3 accumulationOncogenic signalingOncogenic transformationGene expressionInducible activationPharmacological Targeting of PI3K-Dependent Central Tolerance Mechanisms in Refractory Pre-Germinal Center B-Cell Malignancies
Kume K, Lee J, Chan L, Robinson M, Cosgun K, Meffre E, Müschen M. Pharmacological Targeting of PI3K-Dependent Central Tolerance Mechanisms in Refractory Pre-Germinal Center B-Cell Malignancies. Blood 2021, 138: 2267. DOI: 10.1182/blood-2021-149806.Peer-Reviewed Original ResearchCentral tolerance mechanismsMantle cell lymphomaB-cell malignanciesAutoreactive B cellsB cellsB cell developmentB cell receptorEarly B cell developmentB-ALLClinical cohortPharmacological targetingPathological signalingU-CLLNormal B-cell activationAutoreactive B cell receptorsRefractory B-ALLSequential treatment regimensPI3KNegative B cell selectionChronic lymphocytic leukemiaLarge clinical cohortB cell activationB-cell tumorsHuman B lymphopoiesisB cell selection
2019
Signaling Input from Divergent Pathways Subverts Malignant B-Cell Transformation
Chan L, Murakami M, Caesar R, Hurtz C, Kume K, Sadras T, Shojaee S, Pölönen P, Ugale A, Lee J, Cosgun K, Geng H, Heinäniemi M, Lohi O, Wiita A, Izraeli S, Weinstock D, Müschen M. Signaling Input from Divergent Pathways Subverts Malignant B-Cell Transformation. Blood 2019, 134: 3944. DOI: 10.1182/blood-2019-130774.Peer-Reviewed Original ResearchB-cell transformationPrincipal oncogenic driverMalignant B-cell transformationOncogenic driversMalignant transformationNormal B cellsDrug-resistant cancersCentral oncogenic driverCurrent treatmentB cellsPharmacological reactivationSingle oncogenic pathwaySmall molecule agonistsSurface receptorsAdvisory CommitteeB cell receptorERK signal pathwayNormal B cell developmentTreatment responseRare caseDivergent signaling pathwaysSolid tumorsB cell developmentFatal diseaseMolecule agonistsDynamic Assembly of a Feedback Complex to Regulate Oncogenic B-Cell Receptor-Signaling
Lee J, Kume K, Chen Z, Xiao G, Cosgun K, Chen L, Chan L, Klemm L, Chen C, Ma N, Chan W, Forman S, Zammarchi F, Van Berkel P, Melnick A, Ngo V, Geng H, Luger S, Litzow M, McManus M, Vaidehi N, Paietta E, Meffre E, Weinstock D, Müschen M. Dynamic Assembly of a Feedback Complex to Regulate Oncogenic B-Cell Receptor-Signaling. Blood 2019, 134: 393. DOI: 10.1182/blood-2019-131270.Peer-Reviewed Original ResearchB-cell malignanciesB-cell leukemiaB cell receptorPoor clinical outcomeTransplant recipientsB cellsCytoplasmic tailClinical outcomesADC therapeuticsFatal diseaseProximity-dependent biotin identificationRefractory B-cell malignanciesPatient-derived xenograft modelsT cell growth factorNormal B cell developmentClinical outcome dataShort cytoplasmic tailHomology-directed repairB-cell receptor signalingCell membrane translocationNF-κB activationInterleukin-2 (IL-2) functionB cell developmentB-cell tumorsGenetic mouse models
2018
IFITM3-Mediated Regulation of Cell Membrane Dynamics Is Essential for Malignant B-Cell Transformation
Lee J, Geng H, Dinson D, Xiao G, Cosgun K, Chan L, Chen Z, Farzan M, Jung J, Wiita A, Muschen M. IFITM3-Mediated Regulation of Cell Membrane Dynamics Is Essential for Malignant B-Cell Transformation. Blood 2018, 132: 552. DOI: 10.1182/blood-2018-99-117472.Peer-Reviewed Original ResearchB cell receptorLipid raftsOncogenic tyrosine kinasesTyrosine kinasePlasma membraneCentral regulatorNormal B-cell receptorType II transmembrane topologyPI3KMalignant B-cell transformationIntracellular N terminusHomotypic cellular aggregationCell membraneCo-receptor CD19Assembly of membraneMRNA levelsLipid raft formationCell membrane dynamicsPotent tumor suppressorDifferent cell typesCholesterol accumulationCell cycle arrestCell receptorEndocytic motifTransmembrane topologyCD25-Dependent Feedback Control of the B-Cell Receptor and Its Oncogenic Mimics in B-Cell Malignancies
Lee J, Kume K, Chen Z, Xiao G, Cosgun K, Chan L, Chen C, Pillai R, Chan W, Forman S, Kwak L, Zammarchi F, Van Berkel P, Weinstock D, Melnick A, Ngo V, Geng H, Luger S, Litzow M, Belot A, Uzel G, McManus M, Paietta E, Meffre E, Muschen M. CD25-Dependent Feedback Control of the B-Cell Receptor and Its Oncogenic Mimics in B-Cell Malignancies. Blood 2018, 132: 776. DOI: 10.1182/blood-2018-99-117553.Peer-Reviewed Original ResearchB cell receptorReceptor chainsB-cell malignanciesNormal B cell developmentT cell receptor signalingB-cell leukemiaHomology-directed repairCell membrane translocationPoor clinical outcomeB cell developmentFeedback regulatorTransplant recipientsNegative feedback regulatorNegative feedback regulationCytoplasmic tailClinical outcomesGene expressionMolecule downstreamCytokine receptor chainsBCR signalingT cellsB cell selectionGenetic mouse modelsProliferation signalsAstra Zeneca
2016
CD25 Enables Oncogenic BCR Signaling and Represents a Therapeutic Target in Refractory B Cell Malignancies
Lee J, Geng H, Chen Z, Klemm L, Cosgun K, Xiao G, Masouleh B, Hurtz C, Parekh S, Kornblau S, Melnick A, Abbas A, Paietta E, Müschen M. CD25 Enables Oncogenic BCR Signaling and Represents a Therapeutic Target in Refractory B Cell Malignancies. Blood 2016, 128: 4088. DOI: 10.1182/blood.v128.22.4088.4088.Peer-Reviewed Original ResearchB-cell malignanciesB-cell tumorsB cell receptorPoor clinical outcomeCell tumorsCell malignanciesClinical outcomesCD25 expressionB-cell leukemiaT cellsClinical cohortCell leukemiaTherapeutic targetB cellsRefractory B-cell malignanciesCell receptorExpression levelsMultiple B-cell malignanciesTumor clonesRegulatory T cellsHigh expression levelsDivergent clinical outcomesBCR signalingHuman B-cell malignanciesB-cell lymphoma cells