Hepcidin-mediated regulation of iron metabolism in Myelodysplastic syndrome

Abstract

Continuous red blood cell (RBC) transfusions are the main factor of hemosiderosis development, but many Myelodysplastic syndrome (MDS) patients develop iron overload at an early stage of the disease before the red blood cell (RBC) transfusions begin. Hepsidin is a hormone, produced by hepatocytes. It plays a leading role in iron hemostasis. MDS patients demonstrate elevated serum ferritin and hepcidin concentrations even before the RBC transfusions initiating. After 6 months of follow-up, serum ferritin concentration was increased up to 1278 µg/L without significant hepcidin concentration elevation. After 12 months, serum ferritin continued increasing up to 1898 µg/L with a significant hepcidin level decrease to 92±17 pg/ml. The patients group with a ferritin level above average after 12 months of treatment demonstrated significantly lower 5-year overall survival (OS) compared to the group with ferritin level after 12 months of treatment below 1598 µg/L: 5-year OS 9,1±8,7%; median OS – 1,7 years, median observation time 2,9 years (1,2–5,8) in the first group versus 5-year OS 44,4±17,0%; median OS – 4,5 years, median observation time 4,5 years (2,6–6) in the second one. This study findings demonstrating invert correlation of ferritin/hepcidin serum concentration may give evidence to the fact of functional hepatocytes reserves depletion and increased iron deposition in the liver. Altered hepcidin production may be a reason for the hemosiderosis over-progression that is negative for the patients’ quality of life. Serum hepcidin and ferritin concentrations must be assessed every 3 months for the iron helators could be administrated on time.