Effect of iron chelation therapy on EPO-STAT5 signalling pathway and EPO resistance in iron-overloaded low-risk myelodysplastic syndrome patients

Hematology. 2020 Dec;25(1):1-10. doi: 10.1080/16078454.2019.1700330.

Abstract

Objectives: Background/aims: We aim to explore low-risk MDS patients' ESA response and the difference between iron-overloaded (IO) group and the control group in the expression of SOCS1, STAT5 and BCL2L1 which play a key role to EPO-STAT5 signal pathway.Methods: 56 low-risk MDS patients were divided into experimental group, IO patients; control group, non-IO patients. Among experimental group, 28 IO patients were treated with iron chelation therapy (ICT). SOCS1, phosphorylated STAT5 (p-STAT5) and BCL2L1 protein concentration in bone marrow supernatant have been analyzed by ELISA, STAT5a+b protein concentration in bone marrow mononuclear cells (BMMC) have been analyzed by Western blot, and mRNA expression of them have been detected in BMMC by RQ-PCR. The percentage of CD71+ cells in BMMC, apoptotic rate of CD71+ cells and ROS expression in CD71+ cells were detected by Flow cytometry.Results: Compared with the control group, the sEPO concentration, the efficacy of ESA and the expression of SOCS1, apoptotic rates of CD71+ cells and ROS expression in CD71+ cells in IO group were increased, the expression of STAT5 and BCL2L1 was reduced. Interestingly, after receiving ICT, some patients with EPO resistance have responded again to ESA treatment, with the decrease of the expression of SOCS1, apoptotic rates of CD71+ cells, ROS expression in CD71+ cells and the increase of the expression of STAT5 and BCL2L1.Conclusion: Iron overload can increase EPO resistance and the expression of SOCS1, inhibit the expression of STAT5 and BCL2L1. ICT could allivation of EPO resistance.

Keywords: BCL2L1; EPO resistance; Iron overload; MDS; SOCS1; STAT5; anaemia.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Chelation Therapy
  • Erythropoietin / metabolism*
  • Female
  • Hematinics / therapeutic use*
  • Humans
  • Iron Chelating Agents / therapeutic use*
  • Iron Overload / complications
  • Iron Overload / drug therapy*
  • Iron Overload / metabolism
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / complications
  • Myelodysplastic Syndromes / drug therapy*
  • Myelodysplastic Syndromes / metabolism
  • STAT5 Transcription Factor / metabolism*
  • Signal Transduction / drug effects
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Hematinics
  • Iron Chelating Agents
  • STAT5 Transcription Factor
  • STAT5A protein, human
  • Tumor Suppressor Proteins
  • Erythropoietin