Aberrant mitochondrial iron distribution and maturation arrest characterize early erythroid precursors in low-risk myelodysplastic syndromes

Sökning: WFRF:(HAST R) > Aberrant mitochondr...

Tehranchi, RaminLund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine (författare)

Early erythroblasts from patients with refractory anemia (RA) and RA with ringed sideroblasts (RARS) show constitutive mitochondrial release of cytochrome c. Moreover, mature erythroblasts in RARS, but not in RA, display aberrant accumulation of mitochondrial ferritin (MtF). We analyzed cytochrome c release, MtF expression, and gene expression during erythrold differentiation in bone marrow cells from myelodysplastic syndrome (MDS) patients and healthy controls. Whereas none or few cultured erythrold cells from healthy individuals and RA patients expressed MtF, those from RARS patients showed MtF expression at an early stage, when cells were CD34(+) and without morphologic signs of erythroid differentiation. The proportion of RARS erythroblasts that were MtF(+) increased further upon in vitro maturation. Moreover, a significant overexpression of mRNA encoding cytochrome c, and proapoptotic Bid and Bax, was seen in freshly isolated cells from MDS patients. Genes involved in erythroid differentiation were also dysregulated in MDS cells. Importantly, GATA-1 expression increased during normal erythroid maturation, but remained low in MDS cultures, indicating a block of erythroid maturation at the transcriptional level. In conclusion, aberrant MtF expression in RARS erythroblasts occurs at a very early stage of erythrold differentiation and is paralleled by an up-regulation of genes involved in this process.

Ingår i:Blood: American Society of Hematology106:1, s. 247-2531528-00200006-4971

Av författaren/redakt...: Tehranchi, Ramin; Invernizzi, R; Grandien, A; Zhivotovsky, B; Fadeel, B; Forsblom, AM; visa fler...; Travaglino, E; Samuelsson, J; Hast, R; Nilsson, L; Cazzola, M; Wibom, R; Hellstrom-Lindbe ...; visa färre...

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Hematologi

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