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
Ifitm3 Is Essential for PI(3,4,5)P3-Dependent B-Cell Activation and Leukemogenesis
Lee J, Xiao G, Cosgun K, Geng H, Ma N, Chan L, Kume K, Nix M, Chen Z, Chen C, Chen J, Khairnar V, Wiita A, Thomas-Tikhonenko A, Farzan M, Diamond M, Jung J, Vaidehi N, Müschen M. Ifitm3 Is Essential for PI(3,4,5)P3-Dependent B-Cell Activation and Leukemogenesis. Blood 2019, 134: 2782. DOI: 10.1182/blood-2019-127615.Peer-Reviewed Original ResearchPoor clinical outcomeB cellsBCR-ABL1Clinical outcomesPI3KAntigen-specific humoral immune responsesAntigen-specific B cell responsesAntiviral effector functionsTime of diagnosisMRNA levelsB cell responsesHumoral immune responseSurface expressionB cell populationsB-cell malignanciesB-cell receptor signalingDependent B cell activationTransplant recipient miceMalignant B-cell transformationB cell activationB cell precursorsColony formation capacityAdvisory CommitteeSrc kinaseB-cell transformation
2018
B-Cell-Specific Diversion of Glucose Carbon Utilization Reveals a Unique Vulnerability in B Cell Malignancies
Xiao G, Chan LN, Klemm L, Braas D, Chen Z, Geng H, Zhang QC, Aghajanirefah A, Cosgun KN, Sadras T, Lee J, Mirzapoiazova T, Salgia R, Ernst T, Hochhaus A, Jumaa H, Jiang X, Weinstock DM, Graeber TG, Müschen M. B-Cell-Specific Diversion of Glucose Carbon Utilization Reveals a Unique Vulnerability in B Cell Malignancies. Cell 2018, 173: 470-484.e18. PMID: 29551267, PMCID: PMC6284818, DOI: 10.1016/j.cell.2018.02.048.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsB-LymphocytesCarbonCell Line, TumorCell SurvivalGlucoseGlucosephosphate DehydrogenaseGlycolysisHumansIkaros Transcription FactorMiceMice, Inbred C57BLMice, Inbred NODOxidative StressPAX5 Transcription FactorPentose Phosphate PathwayPrecursor Cell Lymphoblastic Leukemia-LymphomaProtein Phosphatase 2Proto-Oncogene Proteins c-bcl-2Transcription, GeneticConceptsPentose phosphate pathwayCarbon utilizationSerine/threonine protein phosphatase 2AB-cell transcription factor PAX5Transcription factor Pax5Favor of glycolysisSmall molecule inhibitionPhosphatase 2ATranscriptional repressionRedox homeostasisOncogenic transformationTumor suppressorMolecule inhibitionPP2AGenetic studiesPhosphate pathwayB cell activationEssential roleB-cell malignanciesCell malignanciesB cellsAntioxidant protectionOxidative stressB-cell tumorsCell activation
2013
Bruton′s Tyrosine Kinase Inhibitor Ibrutinib Interferes With Constitutive and Induced Pre-B Cell Receptor Signaling In B-Cell Acute Lymphoblastic Leukemia
Kim E, Koehrer S, Rosin N, Wang Z, Thomas D, Ravandi F, Kornblau S, Kantarjian H, O'Brien S, Estrov Z, Buggy J, Muschen M, Davis R, Burger J. Bruton′s Tyrosine Kinase Inhibitor Ibrutinib Interferes With Constitutive and Induced Pre-B Cell Receptor Signaling In B-Cell Acute Lymphoblastic Leukemia. Blood 2013, 122: 1399. DOI: 10.1182/blood.v122.21.1399.1399.Peer-Reviewed Original ResearchB cell receptorBruton's tyrosine kinasePre-BCR signalingInhibitor ibrutinibCalcium mobilizationCell linesBruton tyrosine kinase inhibitor ibrutinibB-cell acute lymphoblastic leukemiaGene expression profile analysisB-cell acute lymphoblastic leukemia cell linesEffects of ibrutinibAcute lymphoblastic leukemia cell lineAcute lymphoblastic leukemiaCell proliferationKinase inhibitor ibrutinibIntracellular calcium mobilizationLymphoblastic leukemia cell lineBTK inhibitor ibrutinibCalcium flux assaysB cell activationPre-B cell receptor signalingHalf maximal inhibitory concentrationV4 Expression BeadChipSensitive cell linesTyrosine kinase