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

Research output: Contribution to journalArticle

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.

Details

Authors
  • Ramin Tehranchi
  • R Invernizzi
  • A Grandien
  • B Zhivotovsky
  • B Fadeel
  • AM Forsblom
  • E Travaglino
  • J Samuelsson
  • R Hast
  • L Nilsson
  • M Cazzola
  • R Wibom
  • E Hellstrom-Lindberg
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Hematology
Original languageEnglish
Pages (from-to)247-253
JournalBlood
Volume106
Issue number1
Publication statusPublished - 2005
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Hematology/Transplantation (013022014)