title: Decitabine treatment could ameliorate primary iron-overload in myelodysplastic syndrome patients.
abstract: In order to research how does hypomethylating agents ameliorate iron metabolism in myelodysplastic syndrome (MDS), we performed methylation-specific, polymerase chain reaction (MSP), bisulfate genomic sequencing polymerase chain reaction (BSP), quantitative real-time PCR and western blot of hemojuvelin (HJV) and ELISA assay for hepcidin before and after demethylating therapy (decitabine) to determine whether the change of HJV methylation status would have an influence on hepcidin expression. Eleven of 22 MDS patients achieved CR or PR according to IWG criteria (50%). HJV mRNA was induced in decitabine responders (p = .006 comparing pre/post decitabine treatment) but not in non-responders (p = .121). Similarly, hepcidin serum expression increased from 320.77 ± 34.8 μg/L to 366.77 ± 21.90 μg/L (p = .012) in responders but did not significantly change in non-responders (p = .058), while no difference of adjusted serum ferritin (ASF) was found. In conclusion, hypermethylation of HJV promoter region could silence the gene expression and demethylating therapy might ameliorate iron-overload through HJV demethylation.
authors.affiliation: Department of Hematology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University , Shanghai , China.
authors.forename: Gu
authors.initials: G
authors.lastname: Shucheng
authors.forename: Chang
authors.initials: C
authors.lastname: Chunkang
authors.forename: Zhao
authors.initials: Z
authors.lastname: Youshan
authors.forename: Guo
authors.initials: G
authors.lastname: Juan
authors.forename: Fei
authors.initials: F
authors.lastname: Chengming
authors.forename: Zhang
authors.initials: Z
authors.lastname: Xi
authors.forename: Xiao
authors.initials: X
authors.lastname: Chao
authors.forename: Li
authors.initials: L
authors.lastname: Xiao
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D055396:Bone Morphogenetic Protein 2 / Q000502:physiology; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors*; D000077209:Decitabine; D005260:Female; D005293:Ferritins / Q000097:blood; D058851:GPI-Linked Proteins / Q000235:genetics; D000071020:Hemochromatosis Protein; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D019190:Iron Overload / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000378:metabolism
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D058851:GPI-Linked Proteins; C481006:HJV protein, human; D000071020:Hemochromatosis Protein; D006454:Hemoglobins; D000077209:Decitabine; D005293:Ferritins; D015254:DNA Modification Methylases; D001374:Azacitidine
keywords: Demethylation; HJV; Hepcidin; Myelodysplastic syndromes (MDS); Primary iron overload