Metabolic Determinants of Ferroptosis in B-Cell Lymphoma (ASH 2024) - Nov 6, 2024 - Abstract #976; Pres time: Dec 9, 2024; 05:15 PM - 05:30 PM; Location: Marriott Grand Ballroom 11-13 (Marriott Marquis San Diego Marina); "Background and Significance : Approaches for targeted elimination of B-cells as the root-cause of disease have been highly effective in the treatment of B-cell lymphoma (rituximab, ibrutinib)...This was the case for multiple classes of ferroptosis inducers, including GPX4 inhibitors (RSL3, ML162, ML210), the cysteine-glutamate antiporter (system xc-, SLC7A11) inhibitor Erastin, and the iron oxidizer and GPX4 inactivator FINO2...This likely reflects the intrinsic dependency of B-cell lymphomas on iron import and PUFA-metabolism, at the cost of increased vulnerability to ferroptosis. Furthermore, our CRISPR screens performed with the ferroptosis inducers RSL3, Erastin, and FINO2 revealed phosphatidylcholine synthesis (FLVCR1, PCYT1A) and lipid membrane remodelling (ATP8B2) as central mechanistic targets in B-cell lymphomas."
IO biomarker • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Metabolic Disorders • Non-Hodgkin's Lymphoma • Oncology • Solid Tumor • ACSL3 • ACSL4 • BCL2 • GPX4 • MYC • SLC7A11
|
|
Etienne Leveille, MD1; Eden Bramson1; Mark E Robinson, PhD1; Thierry Bertomeu, PhD2; Andrew Chatr-Aryamontri, PhD2; Shalin Kothari, MD1; Markus Müschen, MD1
|