Despite some advances in the treatment of acute lymphoblastic (ALL) and myeloid leukemia (AML) in recent years, there is still a prominent percentage of pediatric patients with a reduced overall prognosis. Therefore, other therapeutic approaches are needed to treat those patients. In the present study, we report that the metal chelator TPEN affected ΔΨ_m and DNA content in isolated CD34⁺ refractory cells from bone marrow ALL (n = 7; B-cell, n = 4; T-cell, n = 3) and AML (n = 3) pediatric patients. Furthermore, TPEN induced oxidation of hydrogen peroxide (H₂O₂) sensor protein DJ-1, induced up-regulation of BH3-only pro-apoptotic protein PUMA, transcription factor p53 and activated the executor protease CASPASE-3 as apoptosis markers, and reduced the reactivity of the cellular proliferating marker Ki-67 in all acute leukemic groups, and reduced the phosphorylation of c-ABL protein signal in an AML case. Remarkably, bone marrow cells from non-leukemic patients’ cells (n = 2) displayed neither loss of ΔΨ_m nor loss of DNA content when exposed to TPEN. We conclude that TPEN selectively induces apoptosis in acute leukemic cells via reactive oxygen species (ROS) signaling mechanism. Understanding the pathways of TPEN-induced cell death may provide insight into more effective therapeutic ROS-inducing anticancer agents.

尽管近年来急性淋巴细胞 (ALL) 和髓细胞白血病 (AML) 的治疗取得了一些进展，但仍有很大比例的儿科患者总体预后较差。因此，需要其他治疗方法来治疗这些患者。在本研究中，我们报告金属螯合剂 TPEN 影响骨髓 ALL（n = 7；B 细胞，n = 4；T 细胞，n = 3）中分离的 CD34 ⁺难治细胞中的ΔΨ _m和 DNA 含量，并且AML (n = 3) 儿科患者。此外，TPEN 诱导过氧化氢（H ₂ O ₂) 传感蛋白 DJ-1，诱导 BH3-only 促凋亡蛋白 PUMA、转录因子 p53 的上调并激活作为凋亡标志物的执行蛋白酶 CASPASE-3，并降低细胞增殖标志物 Ki-67 的反应性急性白血病组，并降低 AML 病例中 c-ABL 蛋白信号的磷酸化。值得注意的是，来自非白血病患者细胞（n = 2）的骨髓细胞在暴露于 TPEN 时既没有表现出 ΔΨ _{m 的}损失，也没有表现出 DNA 含量的损失。我们得出结论，TPEN 通过活性氧 (ROS) 信号传导机制选择性地诱导急性白血病细胞凋亡。了解 TPEN 诱导的细胞死亡的途径可能有助于深入了解更有效的治疗性 ROS 诱导抗癌剂。