STAT5-Feedback Controls Distinct Metabolic States for Dynamic Transitions between Cellular Activation and Quiescence in Acute Lymphoblastic Leukemia
Kume K, Chen Z, Robinson M, Chan L, Leveille E, Cosgun K, Cheng Z, Arce D, Khanduja D, Graeber T, Müschen M. STAT5-Feedback Controls Distinct Metabolic States for Dynamic Transitions between Cellular Activation and Quiescence in Acute Lymphoblastic Leukemia. Blood 2023, 142: 2977. DOI: 10.1182/blood-2023-191006.Peer-Reviewed Original ResearchB-cell acute lymphoblastic leukemiaAcute lymphoblastic leukemiaLymphoblastic leukemiaPharmacological inhibitionGenetic deletionCellular activationReceptor signalingCell deathBone marrow relapsePoor overall outcomePoor clinical outcomeLeukemia-initiating capacityOncogenic STAT5Mass spectrometry-based metabolomics analysisExpression levelsPhosphorylation of STAT5Flow cytometry analysisMetabolic statePositive MRDRole of mTORMarrow relapseAggressive courseClinical outcomesExcessive protein synthesisMetabolic outcomesCD25 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