Cited by 104Acute Myeloid Leukemia ResearchIron Metabolism and DisordersMitochondrial Function and Pathology

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

Tehranchi, R.·2005·Blood

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 erythroid differentiation in bone marrow cells from myelodysplastic syndrome (MDS) patients and healthy controls. Whereas none or few cultured erythroid 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 erythroid differentiation and is paralleled by an up-regulation of genes involved in this process.

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Crossref · 10.1182/blood-2004-12-4649

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42 of 42 references verified0 citation errors · 0 not checkable

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  • Tf is involved in transport of iron from reticuloendocytic cells and the liver to proliferative cells throughout the body, thereby controlling levels of labile iron.

    “Tf is also involved in the transport of iron from reticuloendocytic cells [red blood cell (RBC) recycling] and the liver to proliferative cells throughout the body, thereby controlling the levels of “labile iron” (293).”

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Authors
Tehranchi, R.
Affiliations
Karolinska University Hospital (SE)
Corresponding author
Tehranchi, R.
Venue
Blood
Published
2005-03-15
Volume
106
Issue
1
Pages
247-253
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
OpenAlex
W2127054377
Cited by
104
References
42
Citations by year
2026: 2 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 4 · 2020: 4 · 2019: 4 · 2018: 3 · 2017: 1 · 2016: 3 · 2015: 2 · 2014: 7 · 2013: 3 · 2012: 3
FWCI
6.30
Type
journal article
Language
en
Open access
closed
Locations
  • Blood (publishedVersion)
  • PubMed (publishedVersion)
  • Lund University Publications (Lund University) (submittedVersion)
Topics
  • Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Keywords
myelodysplastic syndrome, ring sideroblasts, refractory anemia, erythroid precursors, mitochondrial ferritin, cytochrome c release, erythroid differentiation, GATA-1, Bid, Bax, apoptosis, low-risk MDS
MeSH terms
Adenosine Triphosphate, Anemia, Sideroblastic, Carrier Proteins, DNA-Binding Proteins, Erythroblasts, Ferritins, Glycoproteins, Hematopoietic Stem Cells, Hemoglobins, Humans, Iron, Mitochondria, Myelodysplastic Syndromes, Risk Factors, RNA, Messenger, Transcription Factors, Gene Expression, Granulocyte Colony-Stimulating Factor, Apoptosis, Proto-Oncogene Proteins c-bcl-2, Cytochromes c, Erythroid-Specific DNA-Binding Factors, GATA1 Transcription Factor, BH3 Interacting Domain Death Agonist Protein, bcl-2-Associated X Protein

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