In support of a transcriptional mechanism, we further observed that stromal contact significantly upregulated the expression of nuclear factor erythroid 2–related factor 2 (NRF2), a master regulator of GPX4, GCLC, and xCT, in CLL cells (Supplementary Fig. 2e).22 Similar protective effects were observed when CLL cells were cocultured with the alternative bone marrow stromal cell line HS-27A, where ML162-induced specific cell death and lipid peroxidation were likewise reduced, accompanied by a significant increase in the concentration of intracellular thiols (Supplementary Fig. 2f–h). This evidence concerns the gene GCLC and B-cell chronic lymphocytic leukemia.