Mitochondrial ferritin expression in erythroid cells from patients with sideroblastic anemia - PubMed

Affiliations

• PMID: 12406866
• DOI: 10.1182/blood-2002-07-2006

Free article

Mitochondrial ferritin expression in erythroid cells from patients with sideroblastic anemia

Mario Cazzola et al. Blood. 2003.

Free article

Abstract

The sideroblastic anemias are characterized by ring sideroblasts, that is, red cell precursors with mitochondrial iron accumulation. We therefore studied the expression of mitochondrial ferritin (MtF) in these conditions. Erythroid cells from 13 patients with refractory anemia with ring sideroblasts (RARS) and 3 patients with X-linked sideroblastic anemia (XLSA) were analyzed for the distribution of cytoplasmic H ferritin (HF) and MtF using immunocytochemical methods. We also studied 11 healthy controls, 5 patients with refractory anemia without ring sideroblasts (RA), and 7 patients with RA with excess of blasts (RAEB). About one fourth of normal immature red cells, mostly proerythroblasts and basophilic erythroblasts, showed diffuse cytoplasmic positivity for HF, but very few were positive for MtF (0%-10%). Similar patterns were found in anemic patients without ring sideroblasts. In contrast, many erythroblasts from patients with sideroblastic anemia (82%-90% in XLSA and 36%-84% in RARS) were positive for MtF, which regularly appeared as granules ringing the nucleus. Double immunocytochemical staining confirmed the different cellular distribution of HF and MtF. There was a highly significant relationship between the percentage of MtF(+) erythroblasts and that of ring sideroblasts (Spearman R = 0.90; P <.0001). Reverse transcription-polymerase chain reaction studies demonstrated the presence of MtF mRNA in circulating reticulocytes of 2 patients with XLSA but not in controls. These findings suggest that most of the iron deposited in perinuclear mitochondria of ring sideroblasts is present in the form of MtF and that this latter might be a specific marker of sideroblastic anemia.

Similar articles

• The role of the iron transporter ABCB7 in refractory anemia with ring sideroblasts.

  Boultwood J, Pellagatti A, Nikpour M, Pushkaran B, Fidler C, Cattan H, Littlewood TJ, Malcovati L, Della Porta MG, Jädersten M, Killick S, Giagounidis A, Bowen D, Hellström-Lindberg E, Cazzola M, Wainscoat JS. Boultwood J, et al. PLoS One. 2008 Apr 9;3(4):e1970. doi: 10.1371/journal.pone.0001970. PLoS One. 2008. PMID: 18398482 Free PMC article.

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

  Tehranchi R, Invernizzi R, Grandien A, Zhivotovsky B, Fadeel B, Forsblom AM, Travaglino E, Samuelsson J, Hast R, Nilsson L, Cazzola M, Wibom R, Hellström-Lindberg E. Tehranchi R, et al. Blood. 2005 Jul 1;106(1):247-53. doi: 10.1182/blood-2004-12-4649. Epub 2005 Mar 8. Blood. 2005. PMID: 15755901

• Generation and Molecular Characterization of Human Ring Sideroblasts: a Key Role of Ferrous Iron in Terminal Erythroid Differentiation and Ring Sideroblast Formation.

  Saito K, Fujiwara T, Hatta S, Morita M, Ono K, Suzuki C, Fukuhara N, Onishi Y, Nakamura Y, Kawamata S, Shimizu R, Yamamoto M, Harigae H. Saito K, et al. Mol Cell Biol. 2019 Mar 19;39(7):e00387-18. doi: 10.1128/MCB.00387-18. Print 2019 Apr 1. Mol Cell Biol. 2019. PMID: 30670569 Free PMC article.

• Refractory anemia with ring sideroblasts.

  Malcovati L, Cazzola M. Malcovati L, et al. Best Pract Res Clin Haematol. 2013 Dec;26(4):377-85. doi: 10.1016/j.beha.2013.09.005. Epub 2013 Oct 1. Best Pract Res Clin Haematol. 2013. PMID: 24507814 Review.

• Refractory anemia with ring sideroblasts (RARS) and RARS with thrombocytosis: "2019 Update on Diagnosis, Risk-stratification, and Management".

  Patnaik MM, Tefferi A. Patnaik MM, et al. Am J Hematol. 2019 Apr;94(4):475-488. doi: 10.1002/ajh.25397. Epub 2019 Jan 24. Am J Hematol. 2019. PMID: 30618061 Free PMC article. Review.

Cited by

• Characterization of mitochondrial ferritin in Drosophila.

  Missirlis F, Holmberg S, Georgieva T, Dunkov BC, Rouault TA, Law JH. Missirlis F, et al. Proc Natl Acad Sci U S A. 2006 Apr 11;103(15):5893-8. doi: 10.1073/pnas.0601471103. Epub 2006 Mar 29. Proc Natl Acad Sci U S A. 2006. PMID: 16571656 Free PMC article.

• Mitochondrial iron metabolism and its role in neurodegeneration.

  Horowitz MP, Greenamyre JT. Horowitz MP, et al. J Alzheimers Dis. 2010;20 Suppl 2(Suppl 2):S551-68. doi: 10.3233/JAD-2010-100354. J Alzheimers Dis. 2010. PMID: 20463401 Free PMC article. Review.

• Glutaredoxin 5 deficiency causes sideroblastic anemia by specifically impairing heme biosynthesis and depleting cytosolic iron in human erythroblasts.

  Ye H, Jeong SY, Ghosh MC, Kovtunovych G, Silvestri L, Ortillo D, Uchida N, Tisdale J, Camaschella C, Rouault TA. Ye H, et al. J Clin Invest. 2010 May;120(5):1749-61. doi: 10.1172/JCI40372. Epub 2010 Apr 1. J Clin Invest. 2010. PMID: 20364084 Free PMC article.

• The role of the iron transporter ABCB7 in refractory anemia with ring sideroblasts.

  Boultwood J, Pellagatti A, Nikpour M, Pushkaran B, Fidler C, Cattan H, Littlewood TJ, Malcovati L, Della Porta MG, Jädersten M, Killick S, Giagounidis A, Bowen D, Hellström-Lindberg E, Cazzola M, Wainscoat JS. Boultwood J, et al. PLoS One. 2008 Apr 9;3(4):e1970. doi: 10.1371/journal.pone.0001970. PLoS One. 2008. PMID: 18398482 Free PMC article.

• Mitochondrial iron trafficking and the integration of iron metabolism between the mitochondrion and cytosol.

  Richardson DR, Lane DJ, Becker EM, Huang ML, Whitnall M, Suryo Rahmanto Y, Sheftel AD, Ponka P. Richardson DR, et al. Proc Natl Acad Sci U S A. 2010 Jun 15;107(24):10775-82. doi: 10.1073/pnas.0912925107. Epub 2010 May 21. Proc Natl Acad Sci U S A. 2010. PMID: 20495089 Free PMC article. Review.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Elsevier Science
  • Silverchair Information Systems

• Medical

  • MedlinePlus Health Information

• Molecular Biology Databases

  • GlyGen glycoinformatics resource

• Research Materials

  • NCI CPTC Antibody Characterization Program

• Miscellaneous

  • NCI CPTAC Assay Portal