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 pathwayInhibiting Free Fatty Acid Transport to Improve CAR-T Cell Therapy of Relapsed B-Cell Acute Lymphoblastic Leukemia
Garcia C, Lyons K, Liu T, Iacobucci I, Novak A, Argabright A, Donnelly A, Grandvallet Contreras J, Geng H, Smith S, Zhou X, Müschen M, Dick J, Haines J, D'Alessandro A, Mullighan C, Phang T, Kohler M, Witkowski M. Inhibiting Free Fatty Acid Transport to Improve CAR-T Cell Therapy of Relapsed B-Cell Acute Lymphoblastic Leukemia. Blood 2024, 144: 1446-1446. DOI: 10.1182/blood-2024-201015.Peer-Reviewed Original ResearchB-cell acute lymphoblastic leukemiaB-ALL cell linesCAR-TCAR-T therapyB-ALL cellsAcute lymphoblastic leukemiaHuman B-ALL cell linesTP53-MUTLoss-of-function mutationsTP53 mutationsLymphoblastic leukemiaCD19-directed chimeric antigen receptor T cellsB-ALL diagnosisRelapsed B-ALLRelapsed B-cell acute lymphoblastic leukemiaRelapsed/refractory B-cell acute lymphoblastic leukemiaFree fatty acid transportB cell acute lymphoblastic leukemia cellsChimeric antigen receptor T cellsCD19 CAR-T therapyHigh-risk genetic featuresCAR-T cell therapyAssociated with chemotherapy resistanceResistant to conventional chemotherapyPediatric B-ALL patients