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Effects of mitochondrial ferritin overexpression in normal and sideroblastic erythroid progenitors
Author(s) -
Invernizzi Rosangela,
Travaglino Erica,
Della Porta Matteo G.,
Gallì Anna,
Malcovati Luca,
Rosti Vittorio,
Bergamaschi Gaetano,
Erba Benedetta G.,
Bellistri Francesca,
Bastia Raffaella,
Santambrogio Paolo,
Levi Sonia,
Cazzola Mario
Publication year - 2013
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.12316
Subject(s) - erythropoiesis , sideroblastic anemia , microbiology and biotechnology , transferrin receptor , ferritin , biology , progenitor cell , mitochondrion , ineffective erythropoiesis , transferrin , virology , stem cell , bone marrow , anemia , immunology , medicine , biochemistry
Summary In myelodysplastic syndromes with ring sideroblasts ( MDS ‐ RS ), the iron deposited in the mitochondria of RS is present in the form of mitochondrial ferritin ( FTMT ), but it is unknown whether FTMT overexpression is the cause or the result of mitochondrial iron deposition. Lentivirus FTMT ‐transduced CD 34 + bone marrow cells from seven healthy donors and CD 34 + cells from 24 patients with MDS ‐ RS were cultured according to a procedure that allowed the expansion of high numbers of erythroid progenitors. These cells were used to investigate the possible influence of experimentally‐induced FTMT overexpression on normal erythropoiesis and the functional effects of FTMT in sideroblastic erythropoiesis. In MDS ‐ RS progenitors, FTMT overexpression was associated with reduced cytosolic ferritin levels, increased surface transferrin receptor expression and reduced cell proliferation; FTMT effects were independent of SF 3 B 1 mutation status. Similarly, FTMT overexpressing normal erythroid progenitors were characterized by reduced cytosolic ferritin content and increased CD 71 expression, and also by higher apoptotic rate in comparison with the FTMT ‐ controls. Significantly lower levels of STAT 5 phosphorylation following erythropoietin stimulation were found in both sideroblastic and normal FTMT + erythroid cells compared to the FTMT ‐ cells. In conclusion, experimental overexpression of FTMT may modify mitochondrial iron availability and lead to ineffective erythropoiesis.