title: Iron overload may promote alteration of NK cells and hematopoietic stem/progenitor cells by JNK and P38 pathway in myelodysplastic syndromes.
abstract: 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.
authors.affiliation: Department of Hematology, Tianjin Medical University General Hospital, No. 154 Anshan West Street, Heping District, Tianjin, 300052, People's Republic of China.
authors.forename: Yanni
authors.initials: Y
authors.lastname: Hua
authors.affiliation: Department of Hematology, Tianjin Medical University General Hospital, No. 154 Anshan West Street, Heping District, Tianjin, 300052, People's Republic of China.
authors.forename: Chaomeng
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Hematology, Tianjin Medical University General Hospital, No. 154 Anshan West Street, Heping District, Tianjin, 300052, People's Republic of China.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Hematology, Tianjin Medical University General Hospital, No. 154 Anshan West Street, Heping District, Tianjin, 300052, People's Republic of China.
authors.forename: Yihao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Hematology, Tianjin Medical University General Hospital, No. 154 Anshan West Street, Heping District, Tianjin, 300052, People's Republic of China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Hematology, Tianjin Medical University General Hospital, No. 154 Anshan West Street, Heping District, Tianjin, 300052, People's Republic of China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Hematology, Tianjin Medical University General Hospital, No. 154 Anshan West Street, Heping District, Tianjin, 300052, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Hematology, Tianjin Medical University General Hospital, No. 154 Anshan West Street, Heping District, Tianjin, 300052, People's Republic of China.
authors.forename: Zonghong
authors.initials: Z
authors.lastname: Shao
authors.affiliation: Department of Hematology, Tianjin Medical University General Hospital, No. 154 Anshan West Street, Heping District, Tianjin, 300052, People's Republic of China. florai@sina.com.
authors.forename: Rong
authors.initials: R
authors.lastname: Fu
mesh_terms: D000328:Adult; D000368:Aged; D018952:Antigens, CD34; D018450:Disease Progression; D005260:Female; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D019190:Iron Overload / Q000150:complications* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D015470:Leukemia, Myeloid, Acute / Q000209:etiology* / Q000235:genetics*; D020935:MAP Kinase Signaling System; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000209:etiology* / Q000235:genetics* / Q000276:immunology; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D018952:Antigens, CD34; D017382:Reactive Oxygen Species
keywords: Iron overload; JNK; Myelodysplastic syndromes; P38MAPK