Iron chelation: an adjuvant therapy to target metabolism, growth and survival of murine PTEN-deficient T lymphoma and human T lymphoblastic leukemia/lymphoma
Iron chelation: an adjuvant therapy to target metabolism, growth and survival of murine PTEN-deficient T lymphoma and human T lymphoblastic leukemia/lymphoma
复制标题
DOI：
10.1080/10428194.2016.1239257
复制
发表时间：
2017-06-01
影响因子：
2.6
通讯作者：
Peyron, Jean-Francois
中科院分区：
文献类型：
--
作者：
Benadiba, Joy;Rosilio, Celia;Peyron, Jean-Francois
铁是一种基本的营养物质，是新陈代谢反应的催化剂，而新陈代谢反应是细胞生存和增殖的基础。铁与转铁蛋白络合后，通过CD71表面受体内吞作用进入新陈代谢。我们发现，小鼠PTEN缺陷型T细胞淋巴瘤模型和T细胞急性淋巴细胞白血病/淋巴瘤(T-ALL/T-LL)细胞系转化的细胞高表达CD71。结果，细胞对铁成瘾，去铁胺(DFO)对铁的螯合作用极大地影响了细胞的存活，从而诱导了细胞凋亡。有趣的是，DFO与三种ALL特异性药物：地塞米松、阿霉素和L-天冬酰胺酶显示出协同作用。DFO似乎通过依赖于活性氧的DNA损伤反应来发挥作用，并增强了DNA修复的PARP途径抑制物的作用。我们的结果表明，靶向铁代谢可能是一种有趣的急性淋巴细胞白血病的辅助治疗方法。
Iron is an essential nutrient, acting as a catalyst for metabolic reactions that are fundamental to cell survival and proliferation. Iron complexed to transferrin is delivered to the metabolism after endocytosis via the CD71 surface receptor. We found that transformed cells from a murine PTEN-deficient T-cell lymphoma model and from T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/T-LL) cell lines overexpress CD71. As a consequence, the cells developed an addiction toward iron whose chelation by deferoxamine (DFO) dramatically affected their survival to induce apoptosis. Interestingly, DFO displayed synergistic activity with three ALL-specific drugs: dexamethasone, doxorubicin, and L-asparaginase. DFO appeared to act through a reactive oxygen species-dependent DNA damage response and potentiated the action of an inhibitor of the PARP pathway of DNA repair. Our results demonstrate that targeting iron metabolism could be an interesting adjuvant therapy for acute lymphoblastic leukemia.