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

Tehranchi, Ramin LU ; Invernizzi, R; Grandien, A; Zhivotovsky, B; Fadeel, B; Forsblom, AM; Travaglino, E; Samuelsson, J; Hast, R and Nilsson, L, et al. (2005) In Blood 106(1). p.247-253
Abstract
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... (More)
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. (Less)
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publishing date
type
Contribution to journal
publication status
published
subject
in
Blood
volume
106
issue
1
pages
247 - 253
publisher
American Society of Hematology
external identifiers
  • wos:000230156500042
  • pmid:15755901
  • scopus:22044434111
ISSN
1528-0020
DOI
10.1182/blood-2004-12-4649
language
English
LU publication?
yes
id
3e86404e-bb2a-4af7-a453-d7ec87120d6b (old id 233937)
date added to LUP
2007-08-06 10:34:05
date last changed
2017-05-07 03:37:37
@article{3e86404e-bb2a-4af7-a453-d7ec87120d6b,
  abstract     = {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.},
  author       = {Tehranchi, Ramin and Invernizzi, R and Grandien, A and Zhivotovsky, B and Fadeel, B and Forsblom, AM and Travaglino, E and Samuelsson, J and Hast, R and Nilsson, L and Cazzola, M and Wibom, R and Hellstrom-Lindberg, E},
  issn         = {1528-0020},
  language     = {eng},
  number       = {1},
  pages        = {247--253},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Aberrant mitochondrial iron distribution and maturation arrest characterize early erythroid precursors in low-risk myelodysplastic syndromes},
  url          = {http://dx.doi.org/10.1182/blood-2004-12-4649},
  volume       = {106},
  year         = {2005},
}