title: Inappropriately low hepcidin levels in patients with myelodysplastic syndrome carrying a somatic mutation of SF3B1.
abstract: Somatic mutations of the RNA splicing machinery have been recently identified in myelodysplastic syndromes. In particular, a strong association has been found between SF3B1 mutation and refractory anemia with ring sideroblasts, a condition characterized by ineffective erythropoiesis and parenchymal iron overload. We studied the relationship between SF3B1 mutation, erythroid activity and hepcidin levels in myelodysplastic syndrome patients. Erythroid activity was evaluated through the proportion of marrow erythroblasts, soluble transferrin receptor and serum growth differentiation factor 15. Significant relationships were found between SF3B1 mutation and marrow erythroblasts (P=0.001), soluble transferrin receptor (P=0.003) and serum growth differentiation factor 15 (P=0.033). Serum hepcidin varied considerably, and multivariable analysis showed that the hepcidin to ferritin ratio, a measure of adequacy of hepcidin levels relative to body iron stores, was inversely related to the SF3B1 mutation (P=0.013). These observations suggest that patients with SF3B1 mutation have inappropriately low hepcidin levels, which may explain their propensity to parenchymal iron loading.
authors.affiliation: Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Ambaglio
authors.forename: Luca
authors.initials: L
authors.lastname: Malcovati
authors.forename: Elli
authors.initials: E
authors.lastname: Papaemmanuil
authors.forename: Coby M
authors.initials: CM
authors.lastname: Laarakkers
authors.forename: Matteo G
authors.initials: MG
authors.lastname: Della Porta
authors.forename: Anna
authors.initials: A
authors.lastname: Gallì
authors.forename: Matteo C
authors.initials: MC
authors.lastname: Da Vià
authors.forename: Elisa
authors.initials: E
authors.lastname: Bono
authors.forename: Marta
authors.initials: M
authors.lastname: Ubezio
authors.forename: Erica
authors.initials: E
authors.lastname: Travaglino
authors.forename: Riccardo
authors.initials: R
authors.lastname: Albertini
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Campbell
authors.forename: Dorine W
authors.initials: DW
authors.lastname: Swinkels
authors.forename: Mario
authors.initials: M
authors.lastname: Cazzola
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D005260:Female; D005293:Ferritins / Q000097:blood; D064451:Hepcidins / Q000097:blood*; D006801:Humans; D007501:Iron / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000097:blood* / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics*; D000072260:RNA Splicing Factors; D017413:Ribonucleoprotein, U2 Small Nuclear / Q000235:genetics*
chemical_list: D064451:Hepcidins; D010750:Phosphoproteins; D000072260:RNA Splicing Factors; D017413:Ribonucleoprotein, U2 Small Nuclear; C112491:SF3B1 protein, human; D005293:Ferritins; D007501:Iron