Toxic iron species in lower-risk myelodysplastic syndrome patients: course of disease and effects on outcome
Abstract
Red blood cell transfusions (RBCT) remain the cornerstone of supportive care in lower-risk myelodysplastic syndrome (LRMDS). Transfusion dependency in LRMDS patients is associated with inferior outcomes, mainly attributed to severe bone marrow failure.
However, iron toxicity, due to frequent RBCT or ineffective erythropoiesis, may be an additional negative prognostic factor. Recently, much progress has been made in unraveling the iron metabolism.
The peptide hormone hepcidin is the key regulator by inhibiting iron uptake through degradation of ferroportin, a cellular iron exporter. Erythroferrone and GDF15, produced by erythroblasts, inhibit hepcidin production, which leads to increased uptake and cellular release of iron for the purpose of erythropoiesis.
The pathophysiology of iron metabolism in MDS is still not completely understood. Exceedingly high reactive oxygen species (ROS) levels are associated with iron toxicity, disease development, and progression in MDS patients.
Malondialdehyde (MDA), resulting from lipid peroxidation of polyunsaturated fatty acids, is a biomarker of oxidative stress. Currently, little is known about the prognostic impact of ROS in MDS patients.
The aim of this study is twofold: (1) describe iron and oxidative stress parameters over time in LRMDS patients and (2) to assess their effect on overall and progression-free survival.