Iron overload may promote alteration of NK cells and hematopoietic stem/progenitor cells by JNK and P38 pathway in myelodysplastic syndromes
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The objective of the study was to examine levels of intracellular iron, reactive oxygen species (ROS) and the expression of JNK and p38MAPK in NK cells and hematopoietic stem/progenitor cells (HSPCs) in MDS patients, and explore potential mechanisms by which iron overload (IOL) promotes MDS progression. Thirty-four cases of MDS and six cases of AML transformed from MDS (MDS/AML) were included. HSPCs and NK cells were isolated by magnetic absorption cell sorting. We used flow cytometry to detect the levels of ROS and intracellular JNK and P38 in NK cells and HSPCs. Total RNA and protein were extracted from NK cells and CD34+ cells to examine the expression of JNK and p38MAPK using RT-PCR and Western blotting. Intracellular iron concentration was detected. Data were analyzed by SPSS 21 statistical software. Intracellular iron concentration and ROS were increased in both NK cells and HSPCs in MDS patients with iron overload (P < 0.05). MDS patients with iron overload had higher JNK expression and lower p38 expression in NK cells, and higher p38 expression in HSPCs compared with non-iron overload group. IOL may cause alterations in NK cells and HSPCs through the JNK and p38 pathways, and play a role in the transformation to AML from MDS.
KeywordsMyelodysplastic syndromes Iron overload JNK P38MAPK
Yanni Hua, Chaomeng Wang, Huijuan Jiang, Yihao Wang, Chunyan Liu, Lijuan Li, Hui Liu, Zonghong Shao, and Rong Fu, all from the Department of Hematology, Tianjin Medical University General Hospital, made contributions to the manuscript. All authors agreed to the content of the manuscript and its submission to IJH.
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Conflict of interest
All authors have no financial relationship with any organization that sponsored the research. The authors declare no conflicts of interest.
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