Transcriptomic and epigenetic profiling of neuroblastoma states in response to RBM39 degrader.

ABSTRACT: Neuroblastoma accounts for approximately 15% of all pediatric cancer-related deaths, largely due to disease relapse following intensive multimodal therapy. A critical barrier to cure neuroblastoma is the emergence of therapy-resistant tumor cells. Neuroblastoma comprises two major cell states, adrenergic (ADRN) and mesenchymal (MES), which are believed to interconvert and contribute to therapeutic resistance through lineage plasticity. To investigate the mechanisms underlying this plasticity, we subjected human and murine neuroblastoma models to repeated treatment with indisulam, a molecular glue compound that selectively degrades the splicing factor RBM39, until full drug resistance emerged. We then generated datasets from these models, including bulk transcriptomic data, ATAC-seq, and H3

SUBMITTER: Jin H 

PROVIDER: S-EPMC12830888 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature