Targeting CYB561A3 Triggers MYC-Driven Iron Starvation and Lysosomal Damage in Burkitt Lymphoma

This study focuses on the role of CYB561A3 in Burkitt lymphoma (BL), with particular attention to its effects on iron metabolism, cell death, and MYC protein levels. BL is an aggressive B-cell non-Hodgkin's lymphoma characterized by a rearrangement of the MYC gene, which in turn leads to uncontrolled cell proliferation. Using CA46 BL cells, we hypothesized that CYB561A3 knockout (KO) would trigger iron starvation, decrease MYC protein expression, and trigger cell death. The study methods included: determination of iron content by thermochromatography (Thermo Colorimetric Assay), assessment of cell death with the help of Annexin V/PI staining and flow cytometry, measurement of cell viability using MTT assay, and analysis of MYC protein by Western blot. The results showed that CYB561A3 knockdown significantly reduced intracellular iron levels, decreased cell viability, increased apoptosis, and destabilized MYC proteins, thus supporting our hypothesis. These findings highlight the critical dependence of CYB561A3 in BL and provide a rationale for targeting the therapeutic potential of this enzyme in MYC-driven malignancies. Future studies should focus on in vivo validation as well as exploring combination therapies targeting CYB561A3 and MYC.