title: SF3B1-mutated myelodysplastic syndrome with ring sideroblasts harbors more severe iron overload and corresponding over-erythropoiesis.
abstract: OBJECTIVE
  To clarify the possible biological differences and implication of the SF3B1 gene for patients with MDS-RS (myelodysplastic syndromes with ring sideroblasts).
  
  
  METHODS
  Sanger sequencing was performed on mutation hotspots of the SF3B1 gene in MDS-RS patients. The differences between the SF3B1 mutated and wild-type subsets, including the ultrastructure of erythroid precursors, iron profile parameters, erythropoiesis-related measurements, as well as clinical features, were analyzed.
  
  
  RESULTS
  SF3B1 mutations were detected in 33 out of fifty-two MDS-RS patients (63%). The vast majority of patients with mutations (94%) were categorized in the lower risk group according to the IPSS (International Prognostic Scoring System), in contrast to only fifty-eight percent of the wild-type cases. In addition to the notably higher percentages of erythroblasts and ring sideroblasts in patients with mutations, abundant electron-dense granules in the mitochondria of the erythroid precursors were clearly observed. Moreover, patients with mutations presented both improper iron uptake and distribution (lower serum hepcidin-25 concentration, P=0.028) and enhanced erythropoietic activity (higher soluble transferrin receptor level, P=0.132; higher growth differentiation factor 15 concentration, P<0.001). Finally, MDS-RS patients carrying SF3B1 mutations had a better overall survival (median 38 vs. 18 months, P=0.001) compared to those without mutations. By multivariable analysis, the prognostic significance of the SF3B1 mutation was primarily accounted for by IPSS risk categorization.
  
  
  CONCLUSIONS
  MDS-RS patients carrying SF3B1 mutations harbored a more severe iron overload and corresponding over-erythropoiesis. The better overall survival of SF3B1-mutated MDS-RS patients may be mainly due to the clustering of patients with lower risk disease in this group.
authors.affiliation: Department of Haematology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Haematology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. Electronic address: lixiao3326@163.com.
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Haematology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Chunkang
authors.initials: C
authors.lastname: Chang
authors.affiliation: Department of Haematology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
authors.affiliation: Department of Haematology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: He
authors.affiliation: Department of Haematology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Haematology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Tao
authors.affiliation: Department of Haematology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Yizhi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Haematology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Haematology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Shi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000756:Anemia, Sideroblastic / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics; D004920:Erythropoiesis / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019190:Iron Overload / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D010750:Phosphoproteins / Q000235:genetics*; D011379:Prognosis; D000072260:RNA Splicing Factors; D017413:Ribonucleoprotein, U2 Small Nuclear / Q000235:genetics*; D015996:Survival Rate; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D010750:Phosphoproteins; D000072260:RNA Splicing Factors; D017413:Ribonucleoprotein, U2 Small Nuclear; C112491:SF3B1 protein, human
keywords: Erythropoiesis; Iron overload; Myelodysplastic syndrome; Ring sideroblasts; SF3B1 mutation