Immunoglobulin heavy-chain status and stromal interactions shape ferroptosis sensitivity in chronic lymphocytic leukemia.

ABSTRACT: Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of clonal B cells. Although targeted therapies have improved outcomes, resistance remains a challenge, particularly in high-risk patients with TP53 mutations or unmutated immunoglobulin heavy-chain variable region (IGHV) genes (U-CLL). Ferroptosis, a regulated, iron-dependent form of cell death, may represent an exploitable vulnerability in CLL; however, its mechanisms and clinical relevance remain poorly understood. Here, we identified IGHV status and microenvironmental cues as determinants of ferroptosis sensitivity. Using CLL cell lines, patient samples, and in vivo models, we show that CLL cells exhibit elevated basal levels of lipid peroxides and labile iron, predisposing them to ferroptosis. However, stromal inte

SUBMITTER: Bottcher M 

PROVIDER: S-EPMC12765864 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature