GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE309nnn/GSE309171/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE309171GEOGSEfalseNecroptosis serves as a backup for Caspase-8-mediated apoptosis in B cells and blocks lymphomagenesisAlteration of apoptosis is a hallmark of B-cell lymphoma. While mitochondrial apoptosis is critical for lymphomagenesis, the role of extrinsic apoptosis, involving Caspase-8, remains elusive. Caspase-8 initiates apoptosis, suppresses necroptosis, and promotes inflammation independent of cell death. Due to this functional versatility, previous research failed to delineate its role in lymphomagenesis. Here, we demonstrate that B-cell-specific inhibition of Caspase-8 caused an aggressive B-cell malignancy in a subset of mice, resembling human DLBCL. However, most B cells lacking Caspase-8 activity underwent necroptosis, preventing tumor development. Consistently, combined inhibition of Caspase-8 and necroptosis markedly increased lymphoma incidence and mortality. Using both, mouse models and DLBCL patient samples, our study indicates that extrinsic apoptosis and necroptosis act as barriers against lymphomagenesis.2026/09/24GSE309171GSM9262445GSM9262450GSM9262448GSM9262449GSM9262446GSM926244724247309171Mus musculus