Identification of Nuclear NAD+ Salvage As a Therapeutic Vulnerability in B-Lymphoid Malignancies
Robinson M, Li Q, Zhang C, Zhan C, Cheng Z, Kume K, Cosgun K, Kothari S, Agadzhanian N, Nakada D, Müschen M. Identification of Nuclear NAD+ Salvage As a Therapeutic Vulnerability in B-Lymphoid Malignancies. Blood 2024, 144: 4164-4164. DOI: 10.1182/blood-2024-205729.Peer-Reviewed Original ResearchB-ALL cell linesB-ALLB cellsCell linesTherapeutic vulnerabilitiesGene dependenciesNAD+ synthesisMature B-cell lymphomasElimination of B cellsTreatment of B-ALLNAD+ salvageChemotherapy-based regimensEffects of NAMPT inhibitionB-cell depletionB-cell lymphomaB-lymphoid malignanciesB-ALL cellsNAMPT inhibitorsInhibition of NAMPTATP-utilizing enzymesNAD+ salvage pathwayDrug repurposing platformNAD biosynthetic pathwayNear-complete ablationDe novo pathwayIdentification of High-Efficiency β-Catenin Protein Degradation As Critical Vulnerability in B-Cell Malignancies
Cosgun K, Robinson M, Agadzhanian N, Cheng Z, Oulghazi S, Berning P, Fonseca-Arce D, Kume K, Fontaine J, Chan L, Lee J, Yu F, Qian Z, Song J, Chan W, Chen J, Taketo M, Schjerven H, Müschen M. Identification of High-Efficiency β-Catenin Protein Degradation As Critical Vulnerability in B-Cell Malignancies. Blood 2024, 144: 4125-4125. DOI: 10.1182/blood-2024-208125.Peer-Reviewed Original ResearchProtein degradation pathwaysB-ALL cellsProtein degradationRepression of MYCTranscriptional activity of MYCCell deathAcute cell deathLoss of colony formationChIP-seq analysisActive enhancer marksB-cell malignanciesSuper-enhancer regionsActivation of MYCIkaros transcription factorB-lymphoid cellsCell linesB cell identityDefective protein degradationB-cateninNon-lymphoid cell linesDegradation pathwayMantle cell lymphomaProtein levelsB-ALLChIP-seqPKCδ-Mediated Phosphorylation of CD25 Initiates Feedback Control of Oncogenic Tyrosine Kinases in Acute Lymphoblastic Leukemia
Sun R, Lee J, Artadji D, Robinson M, Kume K, Cheng Z, Cosgun K, Chan L, Leveille E, Ma N, Geng H, Paietta E, Vaidehi N, Müschen M. PKCδ-Mediated Phosphorylation of CD25 Initiates Feedback Control of Oncogenic Tyrosine Kinases in Acute Lymphoblastic Leukemia. Blood 2024, 144: 632-632. DOI: 10.1182/blood-2024-211038.Peer-Reviewed Original ResearchB-ALL cellsPatient-derived xenograftsPh+ B-ALLPh-like B-ALLAntibody-drug conjugatesB-ALL casesB-ALLCre-mediated deletionOncogenic tyrosine kinasesBCR-ABL1Tyrosine kinase signalingSurface expressionColony formation capacityCD25 mRNACell surface expression of CD25Tyrosine kinaseGenetic deletionSurface expression of CD25Oncogenic tyrosine kinase signalingKinase signalingOncogene BCR-ABL1Transplant recipient miceControl ADCNegative feedback regulationExpression of CD25