Unknown

Dataset Information

0

Iron Overload Impairs Bone Marrow Mesenchymal Stromal Cells from Higher-Risk MDS Patients by Regulating the ROS-Related Wnt/?-Catenin Pathway.


ABSTRACT: The bone marrow microenvironment plays important roles in the progression of the myelodysplastic syndrome (MDS). The higher incidence of ASXL1 and TET2 gene mutations in our iron overload (IO) MDS patients suggests that IO may be involved in the pathogenesis of MDS. The effects of IO damaging bone marrow mesenchymal stromal cells (MSCs) from higher-risk MDS patients were investigated. In our study, IO decreased the quantity and weakened the abilities of proliferation and differentiation of MSCs, and it inhibited the gene expressions of VEGFA, CXCL12, and TGF-?1 in MSCs regulating hematopoiesis. The increased level of reactive oxygen species (ROS) in MSCs caused by IO might be inducing apoptosis by activating caspase3 signals and involving in MDS progression by activating ?-catenin signals. The damages of MSCs caused by IO could be partially reversed by an antioxidant or an iron chelator. Furthermore, the MSCs in IO MDS/AML patients had increased levels of ROS and apoptosis, and the expressions of caspase3 and ?-catenin were increased even further. In conclusion, IO affects gene stability in higher-risk MDS patients and impairs MSCs by inducing ROS-related apoptosis and activating the Wnt/?-catenin signaling pathway, which could be partially reversed by an antioxidant or an iron chelator.

SUBMITTER: Huang L 

PROVIDER: S-EPMC7648692 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

altmetric image

Publications

Iron Overload Impairs Bone Marrow Mesenchymal Stromal Cells from Higher-Risk MDS Patients by Regulating the ROS-Related Wnt/<i>β</i>-Catenin Pathway.

Huang Lei L   Liu Zhaoyun Z   Liu Hui H   Ding Kai K   Mi Fu F   Xiang Chenhuan C   Wang Guanrou G   Guo Yixuan Y   Fu Rong R  

Stem cells international 20201031


The bone marrow microenvironment plays important roles in the progression of the myelodysplastic syndrome (MDS). The higher incidence of ASXL1 and TET2 gene mutations in our iron overload (IO) MDS patients suggests that IO may be involved in the pathogenesis of MDS. The effects of IO damaging bone marrow mesenchymal stromal cells (MSCs) from higher-risk MDS patients were investigated. In our study, IO decreased the quantity and weakened the abilities of proliferation and differentiation of MSCs,  ...[more]

Similar Datasets

| S-EPMC5600853 | biostudies-literature
| S-EPMC3954514 | biostudies-literature
| S-EPMC6234553 | biostudies-literature
| S-EPMC8776130 | biostudies-literature
| S-EPMC7586162 | biostudies-literature
| S-EPMC5967994 | biostudies-literature
| S-EPMC6913486 | biostudies-literature
| S-EPMC5515705 | biostudies-literature
| S-EPMC6875360 | biostudies-literature
| S-EPMC6716882 | biostudies-literature