PMID- 32380365
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240227
IS  - 1873-5835 (Electronic)
IS  - 0145-2126 (Linking)
VI  - 93
DP  - 2020 Apr 25
TI  - Iron overload regulate the cytokine of mesenchymal stromal cells through 
      ROS/HIF-1alpha pathway in Myelodysplastic syndromes.
PG  - 106354
LID - S0145-2126(20)30059-X [pii]
LID - 10.1016/j.leukres.2020.106354 [doi]
AB  - Iron overload is a significant feature of myelodysplastic syndromes (MDS) 
      patients due to ineffective hematopoiesis and transfusion dependence. Excess iron 
      results in organ dysfunction through the generation of reactive oxygen species 
      (ROS) which can cause oxidative stress even mutation. Mesenchymal stromal cells 
      (MSCs) are responsible for supporting and regulating hematopoiesis, whether MSCs 
      is involved in the pathogenesis of MDS still need further elucidation. 
      Hypoxia-inducible factors-1 (HIF-1) is an integral signal of inflammation that 
      has been shown to up-regulating in MDS patient. We found that MDS-derived MSC had 
      disorganized clones and increased level of apoptosis (n = 53). Iron 
      transportation-related gene, such as DMT1 and ZIP14, and ROS level were increased 
      in iron overload-MDS-MSC (n = 23). HIF-1a, as a crucial part of HIF-1, was also 
      elevated in iron overload-group and PHD2 involved in the degradation of HIF-1a 
      was reduced. Furthermore, HIF-1 downstream cytokines such IL-6, IL-8, TGF-betaand 
      VEGF that were also involved in the pathogenesis of MDS were increased in 
      IO-MDS-MSC. When treated with DFO and NAC for iron chelation and antioxidation, 
      the level of HIF-1a and related cytokines could decrease. We conclude that iron 
      overload regulates the cytokine of mesenchymal stromal cells through ROS/HIF-1alpha 
      pathway in Myelodysplastic syndromes, result in dysfunction of MSC and damage of 
      microenvironment that may be involved in the pathogenesis of MDS.
CI  - Copyright (c) 2020. Published by Elsevier Ltd.
FAU - Hu, Jiaxin
AU  - Hu J
AD  - Department of Hematology, Taianjin Medical University General Hospital, 154 
      Anshan Street, Heping District, Tianjin 300070, PR China.
FAU - Meng, Fanqiao
AU  - Meng F
AD  - Department of Hematology, Taianjin Medical University General Hospital, 154 
      Anshan Street, Heping District, Tianjin 300070, PR China.
FAU - Hu, Xian
AU  - Hu X
AD  - Department of Hematology, Taianjin Medical University General Hospital, 154 
      Anshan Street, Heping District, Tianjin 300070, PR China.
FAU - Huang, Lei
AU  - Huang L
AD  - Department of Hematology, Taianjin Medical University General Hospital, 154 
      Anshan Street, Heping District, Tianjin 300070, PR China.
FAU - Liu, Hui
AU  - Liu H
AD  - Department of Hematology, Taianjin Medical University General Hospital, 154 
      Anshan Street, Heping District, Tianjin 300070, PR China.
FAU - Liu, Zhaoyun
AU  - Liu Z
AD  - Department of Hematology, Taianjin Medical University General Hospital, 154 
      Anshan Street, Heping District, Tianjin 300070, PR China.
FAU - Li, Lijuanli
AU  - Li L
AD  - Department of Hematology, Taianjin Medical University General Hospital, 154 
      Anshan Street, Heping District, Tianjin 300070, PR China. Electronic address: 
      lilijuan20@qq.com.
LA  - eng
PT  - Journal Article
DEP - 20200425
PL  - England
TA  - Leuk Res
JT  - Leukemia research
JID - 7706787
SB  - IM
OTO - NOTNLM
OT  - Hypoxia inducible factor-1
OT  - Iron overload
OT  - Mesenchymal stromal cells
OT  - Myelodysplastic syndromes
COIS- Declaration of Competing Interest There are no competing interests among authors.
EDAT- 2020/05/08 06:00
MHDA- 2020/05/08 06:01
CRDT- 2020/05/08 06:00
PHST- 2020/03/07 00:00 [received]
PHST- 2020/04/10 00:00 [revised]
PHST- 2020/04/13 00:00 [accepted]
PHST- 2020/05/08 06:01 [medline]
PHST- 2020/05/08 06:00 [pubmed]
PHST- 2020/05/08 06:00 [entrez]
AID - S0145-2126(20)30059-X [pii]
AID - 10.1016/j.leukres.2020.106354 [doi]
PST - aheadofprint
SO  - Leuk Res. 2020 Apr 25;93:106354. doi: 10.1016/j.leukres.2020.106354.