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Deferasirox combination with eltrombopag shows anti-myelodysplastic syndrome effects by enhancing iron deprivation–related apoptosis
  1. Lei Huang,
  2. Mengyue Tian,
  3. Zhaoyun Liu,
  4. Chunyan Liu,
  5. Rong Fu
  1. Hematology, Tianjin Medical University General Hospital, Tianjin, China
  1. Correspondence to Dr Rong Fu, Hematology, Tianjin Medical University General Hospital, Tianjin 300052, China; furong8369{at}tmu.edu.cn

Abstract

Iron overload (IO) affected the survival of patients with myelodysplastic syndrome (MDS). Deferasirox (DFX) is widely used in patients with MDS for iron chelation therapy, but is not suitable for MDS patients with severe thrombocytopenia. Eltrombopag (ELT) is a type of thrombopoietin receptor (TPOR) analog used in the treatment of thrombocytopenia. Therefore, we sought to explore the synergistic effects and possible mechanisms of DFX combination with ELT in MDS cells. In our study, the combination of DFX with ELT synergistically inhibited proliferation, induced apoptosis and arrested cell cycle of MDS cells. Through the RNA-sequence and gene set enrichment analysis (GSEA), iron metabolism–related pathway played important roles in apoptosis of SKM-1 cells treated with DFX plus ELT. Transferrin receptor (TFRC) was significantly highly expressed in combination group than that in single agent groups, without affecting TPOR. Furthermore, the apoptosis of the combination group MDS cells could be partially reversed by ferric ammonium citrate (FAC), accompanied with decreased expression of TFRC. These results suggested that the combination of DFX and ELT synergistically induced apoptosis of MDS cells by enhancing iron deprivation–related pathway.

  • iron
  • apoptosis
  • myeloproliferative disorders

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Footnotes

  • LH and MT contributed equally.

  • Contributors MT carried out the molecular genetic studies. ZL and CL participated in the cell culture and performed the statistical analysis. LH carried out the flow cytometry analysis and drafted the manuscript. RF conceived of the study, participated in its design and responsible for the overall content. LH and MT contributed equally to this work. All authors read and approved the final manuscript.

  • Funding This work was supported by the National Natural Science Foundation of China (Grant no. 81770110); National Natural Science Foundation Youth Project of China (Grant no. 81800123 and 81900131); Tianjin Natural Science Foundation (Key Project) (Grant no. 16JCZDJC35300); Tianjin Science and Technology Plan Project (Grant no. 20YFZCSY00060); Tianjin Municipal Natural Science Foundation Youth Project (Grant no. 18JCQNJC80400); Science and Technology Project of Tianjin Health Commission Youth Project (Grant no. QN20006) and the Scientific Research Project of Tianjin Education Commission (Grant nos. 2018KJ043, 2018KJ045 and 2017KJ195).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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