title: Serum iron metabolism and erythropoiesis in patients with myelodysplastic syndrome not receiving RBC transfusions.
abstract: Dysregulation of hepcidin, a key iron regulating hormone, is important in the pathogenesis of iron overload in patients with myelodysplatic syndrome (MDS). However, most studies of hepcidin levels are complicated by concomitant RBC transfusions. To evaluate the relationship between iron metabolism and erythropoiesis, we measured serum levels of hepcidin, growth-differentiation factor-15 (GDF15) and other markers of erythropoiesis in 107 subjects with MDS not receiving RBC transfusions. Patients with MDS had significantly higher levels of hepcidin than normals. However, their hepcidin-ferritin ratio was markedly decreased compared to normals (P<0.001) and varied substantially between MDS subtypes (P=0.011). GDF15 levels positively correlated with percent of bone marrow erythroblasts (P<0.001), soluble transferrin receptor (sTfR) (P=0.018), and also with transferrin saturation (ISAT) (P=0.038). The hepcidin-ferritin ratio negatively correlated with serum erythropoietin (EPO) levels (P<0.001), and also with GDF15 levels (P=0.014). Colony forming cells (CFC) were evaluated in 70 subjects. Those with serum ferritin (SF) levels <500 ng/ml had significantly more BFU-E than subjects with SF ≥ 500 ng/L (P=0.007), but numbers of granulocyte/macrophage-colony-forming cells (CFU-GM) were similar (P=0.190). Our data indicate serum hepcidin levels are inappropriately low in patients MDS not receiving RBC transfusions. GDF15 levels correlated with low hepcidin levels and may contribute to iron overload in this setting. Iron overload may in turn suppress erythropoiesis by imparing the proliferative capacity of the erythroid progenitor cells.
authors.affiliation: MDS and MPN Centre, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Cui
authors.affiliation: Imperial College London, London, United Kingdom.
authors.forename: Robert Peter
authors.initials: RP
authors.lastname: Gale
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Zhu
authors.affiliation: MDS and MPN Centre, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
authors.forename: Zefeng
authors.initials: Z
authors.lastname: Xu
authors.affiliation: MDS and MPN Centre, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
authors.forename: Tiejun
authors.initials: T
authors.lastname: Qin
authors.affiliation: MDS and MPN Centre, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China; State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Division of Pathology & Divisions of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, United States.
authors.forename: Gang
authors.initials: G
authors.lastname: Huang
authors.affiliation: MDS and MPN Centre, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.affiliation: MDS and MPN Centre, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
authors.forename: Liwei
authors.initials: L
authors.lastname: Fang
authors.affiliation: MDS and MPN Centre, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
authors.forename: Hongli
authors.initials: H
authors.lastname: Zhang
authors.affiliation: MDS and MPN Centre, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Pan
authors.affiliation: MDS and MPN Centre, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
authors.forename: Naibo
authors.initials: N
authors.lastname: Hu
authors.affiliation: MDS and MPN Centre, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
authors.forename: Shiqiang
authors.initials: S
authors.lastname: Qu
authors.affiliation: MDS and MPN Centre, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China; State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China. Electronic address: zjxiao@hotmail.com.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Xiao
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017707:Erythrocyte Transfusion; D004920:Erythropoiesis; D005260:Female; D055436:Growth Differentiation Factor 15 / Q000097:blood; D064451:Hepcidins / Q000097:blood; D006706:Homeostasis; D006801:Humans; D007501:Iron / Q000378:metabolism*; D019190:Iron Overload / Q000097:blood; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000097:blood* / Q000628:therapy
chemical_list: C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D064451:Hepcidins; D007501:Iron
keywords: Hematopoiesis; Iron metabolism; Myelodysplastic syndromes