PDF(Pubmed)
Abstract：
Acute lymphoblastic leukaemia (ALL) is the most prevalent cancer in children, and excessive iron buildup resulting from blood transfusions and chemotherapy potentially has a negative impact on treatment outcomes and prognosis in patients with ALL. Therefore, initiating early iron chelation therapy during ALL treatment is a logical approach. Ideally, the selected iron chelator should also possess anti-leukaemia properties. The aim of the present study was to explore the potential impact and underlying mechanism of deferasirox (DFX) in ALL therapy. This study proved that DFX, an iron chelator, is capable of inducing leukaemia cell death through ferroptosis, which is achievable by increasing the expression of acetylated nuclear factor erythroid 2-related factor 2 (NRF2). More specifically, NRF2 acetylation on Lys599 was facilitated by acetyltransferase-p300/CBP. These findings indicate that DFX could serve as a potent adjunctive medication for patients with ALL. Moreover, DFX may offer dual benefits in ALL treatment, functioning as both an iron chelator and NRF2-modulating agent. Further research and clinical trials are necessary to fully elucidate the therapeutic potential of DFX in patients with ALL and incorporate it into treatment protocols.
摘要：
急性淋巴细胞白血病（ALL）是儿童中最常见的癌症，输血和化疗导致的过量铁积累可能对ALL患者的治疗结果和预后产生负面影响.因此,在ALL治疗期间启动早期铁螯合治疗是合乎逻辑的方法.理想情况下,所选择的铁螯合剂也应具有抗白血病特性。本研究的目的是探讨地拉罗司（DFX）在ALL治疗中的潜在影响和潜在机制。这项研究证明了DFX，一种铁螯合剂,能够通过铁凋亡诱导白血病细胞死亡，这是可以通过增加乙酰化的核因子红系2相关因子2（NRF2）的表达来实现的。更具体地说,乙酰转移酶-p300/CBP促进了Lys599上的NRF2乙酰化。这些发现表明DFX可以作为ALL患者的有效辅助药物。此外，DFX可能在所有治疗中提供双重益处，同时充当铁螯合剂和NRF2调节剂。进一步的研究和临床试验是必要的，以充分阐明DFX在ALL患者中的治疗潜力，并将其纳入治疗方案。
