Redox destabilization by ibrutinib promotes ferroptosis in diffuse large B-cell lymphoma (DLBCL).

ABSTRACT: Diffuse large B-cell lymphoma (DLBCL) exhibits marked clinical heterogeneity and frequent treatment resistance, particularly in molecularly defined high-risk subtypes such as ABC-DLBCL. While current therapies largely rely on apoptosis induction, non-apoptotic cell death pathways remain underexplored in hematologic malignancies. Here, we identify ferroptosis, an iron-dependent, lipid peroxidation-driven form of regulated necrosis, as an effective baseline in additive therapy with ibrutinib for the treatment of DLBCL. Transcriptomic and lipidomic analyses revealed that DLBCL cells, despite lacking overt enrichment of polyunsaturated fatty acids (PUFAs), display elevated expression of the core ferroptosis protective machinery. Inhibition of GPX4 induced rapid and selective lipid ROS accumula

SUBMITTER: Langpape A 

PROVIDER: S-EPMC12578790 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature