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
Pharmacological 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
2018
Ras-Driven B-Cell Transformation Targets Developmental Rewiring of Cytokine to Pre-B Cell Receptor Signaling
Chan L, Hurtz C, Geng H, Auer F, Chen Z, Xiao G, Lee J, Cosgun K, Ye B, Muschen M. Ras-Driven B-Cell Transformation Targets Developmental Rewiring of Cytokine to Pre-B Cell Receptor Signaling. Blood 2018, 132: 1336. DOI: 10.1182/blood-2018-99-115514.Peer-Reviewed Original ResearchPre-BCR signalingOncogenic Ras signalingOncogene-induced senescencePotential therapeutic intervention pointsCompetitive growth assaysInducible activationTherapeutic intervention pointCytokine receptorsRas signalingOncogenic RasPre-B cell receptor signalingCell transitionGenetic studiesPre-B cell receptorPre-B cell transitionIrreversible cell cycle arrestEarly B cell developmentLight chain gene expressionCell receptor signalingB cell developmentARF/p53Number of coloniesChain gene expressionDepletion of cellsCell cycle arrestPre-BCR Surrogate Light Chain Components VPREB1 and IGLL1 Function As Pre-BCR-Independent Tumor Suppressors in Acute Lymphoblastic Leukemia
Cosgun K, Hendriks R, Dickins R, Heisterkamp N, Muschen M. Pre-BCR Surrogate Light Chain Components VPREB1 and IGLL1 Function As Pre-BCR-Independent Tumor Suppressors in Acute Lymphoblastic Leukemia. Blood 2018, 132: 570. DOI: 10.1182/blood-2018-99-115522.Peer-Reviewed Original ResearchBCR-ABL1Transgenic miceSurrogate light chainTime of diagnosisTime of relapseDouble transgenic miceExerts tumor-suppressive effectsAcute lymphoblastic leukemiaB cell defectsDay of birthBCR-ABL1 tyrosine kinaseHigh surface levelsTumor-suppressive effectsPre-BCR expressionColony formation abilityPhosphorylation of BtkTumor suppressorBCR-ABL1 oncogeneEarly B cell developmentTumor suppressive functionLymphoblastic leukemiaCell cycle arrestFrequent lesionsSecondary lesionsSuppressive function