Hematology and Stem Cell Transplant Center, Marche Nord Hospital, Pesaro, Italy.
Hematology, Ospedale San Gerardo, Monza, Italy.
Blood Rev. 2018 Nov;32(6):473-479. doi: 10.1016/j.blre.2018.04.004. Epub 2018 Apr 13.
Excess iron can be extremely toxic for the body and may cause organ damage in the absence of iron chelation therapy. Preclinical studies on the role of free iron on bone marrow function have shown that iron toxicity leads to the accumulation of reactive oxygen species, affects the expression of genes coding for proteins that regulate hematopoiesis, and disrupts hematopoiesis. These effects could be partially attenuated by iron-chelation treatment with deferasirox, suggesting iron toxicity may have a negative impact on the hematopoietic microenvironment. Iron toxicity is of concern in transfusion-dependent patients. Importantly, iron chelation with deferasirox can cause the loss of transfusion dependency and may induce hematological responses, although the mechanisms through which deferasirox exerts this action are currently unknown. This review will focus on the possible mechanisms of toxicity of free iron at the bone marrow level and in the bone marrow microenvironment.
过量的铁对身体可能是极其有害的,如果没有铁螯合疗法,可能会导致器官损伤。关于游离铁在骨髓功能中的作用的临床前研究表明,铁毒性会导致活性氧的积累,影响调节造血的蛋白质编码基因的表达,并破坏造血。用地拉罗司进行铁螯合治疗可以部分减轻这些影响,这表明铁毒性可能对造血微环境产生负面影响。铁毒性在依赖输血的患者中引起关注。重要的是,用地拉罗司进行铁螯合治疗可以导致输血依赖性丧失,并可能诱导血液学反应,尽管地拉罗司发挥这种作用的机制目前尚不清楚。这篇综述将重点讨论游离铁在骨髓水平和骨髓微环境中的毒性的可能机制。