伯基特淋巴瘤（BL）是一种高度侵袭性淋巴瘤，主要影响儿童和年轻人。化疗对年轻的 BL 患者有效，但对成人的结果不太令人满意。因此，需要增强BL治疗中使用的药物的细胞毒作用。谷胱甘肽（GSH）是一种重要的抗氧化剂，参与氧化应激调节和药物解毒等过程。在许多癌症中都观察到谷胱甘肽水平升高，并且与化疗耐药相关。我们之前发现 GCLC（编码参与 GSH 生物合成的酶）是 BL 中的必需基因。我们现在证实，GCLC 的敲除会降低 BL 细胞的活力，并且 GCLC 蛋白在 BL 组织中过度表达。此外，我们证明丁硫氨酸亚磺酰亚胺（BSO）是一种已知的 GCLC 抑制剂，可降低 BL 细胞的生长，但不影响对照 B 细胞。此外，我们首次证明 BSO 增强了 BL 治疗中常用的化合物、阿霉素和环磷酰胺的细胞毒性。鉴于 BSO 本身对对照细胞没有毒性，并且在临床试验中具有良好的耐受性，化疗与 BSO 的组合可能会减少 BL 患者获得有效反应所需的细胞毒性药物的剂量。© 2023。作者）。

Burkitt lymphoma (BL) is a highly aggressive lymphoma that mainly affects children and young adults. Chemotherapy is effective in young BL patients but the outcome in adults is less satisfactory. Therefore, there is a need to enhance the cytotoxic effect of drugs used in BL treatment. Glutathione (GSH) is an important antioxidant involved in processes such as regulation of oxidative stress and drug detoxification. Elevated GSH levels have been observed in many cancers and were associated with chemoresistance. We previously identified GCLC, encoding an enzyme involved in GSH biosynthesis, as an essential gene in BL. We now confirm that knockout of GCLC decreases viability of BL cells and that the GCLC protein is overexpressed in BL tissues. Moreover, we demonstrate that buthionine sulfoximine (BSO), a known inhibitor of GCLC, decreases growth of BL cells but does not affect control B cells. Furthermore, we show for the first time that BSO enhances the cytotoxicity of compounds commonly used in BL treatment, doxorubicin, and cyclophosphamide. Given the fact that BSO itself was not toxic to control cells and well-tolerated in clinical trials, combination of chemotherapy with BSO may allow reduction of the doses of cytotoxic drugs required to obtain effective responses in BL patients.© 2023. The Author(s).