2025
Common origins of autoimmune diseases and lymphoid malignancies
Leveille E, Müschen M. Common origins of autoimmune diseases and lymphoid malignancies. Trends In Immunology 2025 PMID: 40816970, PMCID: PMC12360480, DOI: 10.1016/j.it.2025.07.010.Peer-Reviewed Original ResearchLymphoid malignanciesAutoimmune diseasesRisk of lymphoma developmentDevelopment of autoimmune diseasesT-cell lymphomaDevelopment of lymphoid malignanciesMechanism of negative selectionAutoimmune manifestationsLymphoma developmentAutoreactive lymphocytesT cellsAutoimmune disordersAdaptive immunityMalignancyGenetic lesionsLymphocyte developmentPathological lymphocytesLymphocytesDisease typeDiseaseNegative selection
2023
Repurposing GSK3B Small Molecule Inhibitors for Refractory Lymphoid Malignancies
Cosgun K, Robinson M, Oulghazi S, Xu L, Xiao G, Chan L, Lee J, Kume K, Leveille E, Arce D, Khanduja D, Feldhahn N, Song J, Chan W, Chen J, Taketo M, Schjerven H, Jellusova J, Kothari S, Davids M, Müschen M. Repurposing GSK3B Small Molecule Inhibitors for Refractory Lymphoid Malignancies. Blood 2023, 142: 2818. DOI: 10.1182/blood-2023-190522.Peer-Reviewed Original ResearchFavorable safety profileSmall molecule inhibitorsT-lymphoid malignancyΒ-catenin degradationLymphoid malignanciesΒ-cateninInteractome studiesSafety profileClinical trialsMolecule inhibitorsLow nanomolar concentrationsΒ-catenin accumulationSolid tumorsRefractory B-cell malignanciesCell deathPK/PD profilesZinc finger proteinRefractory lymphoid malignanciesChIP-seq analysisPhase 2 trialMYC target genesT-cell lymphomaColony formationRapid nuclear accumulationWnt/β-catenin pathwayPD-1 instructs a tumor-suppressive metabolic program that restricts glycolysis and restrains AP-1 activity in T cell lymphoma
Wartewig T, Daniels J, Schulz M, Hameister E, Joshi A, Park J, Morrish E, Venkatasubramani A, Cernilogar F, van Heijster F, Hundshammer C, Schneider H, Konstantinidis F, Gabler J, Klement C, Kurniawan H, Law C, Lee Y, Choi S, Guitart J, Forne I, Giustinani J, Müschen M, Jain S, Weinstock D, Rad R, Ortonne N, Schilling F, Schotta G, Imhof A, Brenner D, Choi J, Ruland J. PD-1 instructs a tumor-suppressive metabolic program that restricts glycolysis and restrains AP-1 activity in T cell lymphoma. Nature Cancer 2023, 4: 1508-1525. PMID: 37723306, PMCID: PMC10597841, DOI: 10.1038/s43018-023-00635-7.Peer-Reviewed Original ResearchConceptsPD-1T-NHLAP-1 activityT-cell non-Hodgkin lymphomaImmune checkpoint receptor PD-1Cell non-Hodgkin lymphomaCheckpoint receptor PD-1Receptor PD-1Non-Hodgkin lymphomaT-cell lymphomaT-cell malignanciesPrimary patient samplesTractable mouse modelAdvanced diseaseInferior prognosisProtein-1 transcription factorT cellsCell lymphomaMouse modelCell malignanciesATP citrate lyase activityACLY inhibitionPatient samplesTumor suppressive mechanismKey tumor suppressor
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