{"database":"ENA","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"center_name":["Knight Cancer Institute, Oregon Health and Science University"],"full_dataset_link":["https://www.ebi.ac.uk/ena/browser/view/PRJNA576383"],"scientific_name":["Homo sapiens"],"long_description":["Novel targeted agents used in therapy of lymphoid malignancies, such as inhibitors of B-cell receptor-associated kinases, are recognized to have complex immune-mediated effects. NEDD8-activating enzyme (NAE) has been identified as a tractable target in chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma. We and others have shown that pevonedistat (TAK-924), a small molecule inhibitor of NAE, abrogates NF-κB signaling in malignant B cells. However, NF-κB pathway activity is indispensable in immune response, and T-cell function is altered in patients with CLL. Using T cells derived from patients with CLL, we demonstrate that while targeting NAE results in markedly differential expression of NF-κB-regulated genes and downregulation of IL-2 signaling during T-cell activation, T cells evade apoptosis. Meanwhile, NAE inhibition favorably modulates polarization of T cells in vitro, with decreased Treg differentiation and a shift towards TH1 phenotype, accompanied by increased interferon-γ production. These findings were recapitulated in vivo in immunocompetent mouse models. T cells exposed to pevonedistat in washout experiments, informed by its human pharmacokinetic profile, recover NAE activity and maintain their response to T-cell receptor stimulation and cytotoxic potential. Our data shed light on the potential immune implications of targeting neddylation in CLL and lymphoid malignancies. Overall design: Isolated primary T cells were stimulated and treated with either pevonedistat or vehicle (DMSO) at 3hrs and 24 hrs with 4 replicates."],"repository":["ENA"],"additional_accession":[]},"is_claimable":false,"name":"Expression profiling of CLL derived T Cells treated with pevonedistat","description":"Expression profiling of CLL derived T Cells treated with pevonedistat","dates":{"last_updated":"2025-09-24","first_public":"2019-10-10"},"accession":"PRJNA576383","cross_references":{"GEO":["GSE138560"],"taxon":["9606"]}}