RT Journal Article
SR Electronic
T1 Deferasirox combination with eltrombopag shows anti-myelodysplastic syndrome effects by enhancing iron deprivation–related apoptosis
JF Journal of Investigative Medicine
JO J Investig Med
FD BMJ Publishing Group Ltd
SP 953
OP 962
DO 10.1136/jim-2021-002147
VO 70
IS 4
A1 Lei Huang
A1 Mengyue Tian
A1 Zhaoyun Liu
A1 Chunyan Liu
A1 Rong Fu
YR 2022
UL http://hw-f5-jim.highwire.org/content/70/4/953.abstract
AB 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.The data that support the findings of this study are available from the corresponding author upon reasonable request.