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
2019
Metabolic gatekeepers to safeguard against autoimmunity and oncogenic B cell transformation
Müschen M. Metabolic gatekeepers to safeguard against autoimmunity and oncogenic B cell transformation. Nature Reviews Immunology 2019, 19: 337-348. PMID: 30890785, DOI: 10.1038/s41577-019-0154-3.Peer-Reviewed Original ResearchConceptsB cell receptorAutoreactive B cell receptorsLineage-determining transcription factorsMetabolic gatekeeperMitochondrial ATP productionB-cell transformationTranscription factorsEnergy stressPhosphate pathway activityATP productionCell transformationSmall cytoplasmic volumeCell deathPathway activityB cellsEnergy metabolismCell proliferationCytoplasmic volumeCell receptorGlucose uptakeOncogeneB cell proliferationCellsMetabolic demandsAdditional glucose
2015
Targeted Activation of B Cell Autoimmunity Checkpoints in Acute Lymphoblastic Leukemia
Chen Z, Geng H, Lowell C, Weiss A, Hunger S, Melnick A, Muschen M. Targeted Activation of B Cell Autoimmunity Checkpoints in Acute Lymphoblastic Leukemia. Blood 2015, 126: 3716. DOI: 10.1182/blood.v126.23.3716.3716.Peer-Reviewed Original ResearchTyrosine kinase inhibitorsB cell receptorAcute lymphoblastic leukemiaPre-BCR signalingB cellsB cell selectionLymphoblastic leukemiaBCR-ABL1Autoreactive B cell receptorsCell deathPre-B-cell originAcute lymphoblastic leukemia cellsCurrent therapy approachesLeukemia cellsWorse clinical outcomesSelf-reactive B cellsNegative B cell selectionPotent tyrosine kinase inhibitorLymphoblastic leukemia cellsNovel small molecule inhibitorTypes of cancerUbiquitous self-antigenClinical outcomesIncremental increasePoor outcome