Iron Chelators May Enhance Erythropoiesis by Increasing Iron Delivery to Haematopoietic Tissue and Erythropoietin Response in Iron-Loading Anaemia

Abstract

Based on the mode of action of iron chelators, one might expect a decrease in bone marrow iron availability, resulting in worsening of the anaemia in certain types of iron-loading anaemia. However, improvement of anaemia or reduction in transfusion requirements during chelation treatment has been reported in various types of iron-loading anaemia. It is suggested that iron chelators act as mediators facilitating iron release from storage sites and its delivery to haematopoietic tissues. In addition, a reduction of iron stores may upregulate erythropoietin response and bring about a decrease of disease activity in inflammatory disorders, resulting in a haemoglobin rise. Large trials with (oral) iron chelators are required to verify these possible effects.

Hematologic responses in patients with aplastic anemia treated with deferasirox: a post hoc analysis from the EPIC study

“…One possible hypothesis is that as deferasirox facilitates the Hematologic responses in aplastic anemia patients haematologica | 2013; 98 (7) 1047 reduction in iron stores, erythropoietin production is upregulated, resulting in a rise in hemoglobin. 22 A further possibility is that deferasirox chelation decreases reactive oxygen species generation in the marrow microenvironment, leading to greater genomic stability, as has been suggested in patients with myelodysplastic syndromes. 23 Based on the serum ferritin data in this analysis, hematologic responses were observed in patients with greater reductions in serum ferritin levels, suggesting that hematologic response might be dependent, at least partially, on reductions in levels of body iron overload.…”

Improvement in Hematopoiesis after Iron Chelation Therapy with Deferasirox in Patients with Aplastic Anemia

“…Possible hypotheses include anti-inflammatory effects, e.g. by scavenging tissue-damaging oxygen free radicals, promoting iron release from storage sites by iron chelators thus facilitating its use for hematopoietic tissue, up-regulating the erythropoietin response by decreasing iron stores and thus increasing Hb levels and activating erythropoietin gene transcription [23,24,25,26]. Recent data established that iron overload enhanced the levels of intracellular reactive oxygen species and promoted apoptosis of immature erythroblasts via suppression of BCL2 expression [27].…”

The human counterpart of zebrafish shiraz shows sideroblastic-like microcytic anemia and iron overload

“…22 Indeed GLRX5-deficient yeast, which lacks Fe/S enzyme activity and has mitochondrial iron overload, has increased ROS production. 23 However, ROSs were found normal in shiraz.…”