Fanconi's anemia cells are relatively resistant to H2O2-induced damage

Rosario Notaro, Nunzia Montuori, Carmen Di Grazia, Salvatore Formisano, Bruno Rotoli, Carmine Selleri

Research output: Contribution to journalArticlepeer-review

Abstract

Background and Objective. Fanconi's anemia (FA) is a rare autosomal recessive syndrome characterized by skeletal abnormalities, late onset bone marrow failure and susceptibility to neoplasias. Reduced defense against oxidative stress is thought to be one of the cell damaging mechanisms. We investigated in vitro the effects of oxidative stress on red blood cells (RBC) and on hematopoietic progenitor growth of normal donors and of FA patients. Design and Methods. The effects of hydrogen peroxide (H2O2) on RBC and hematopoietic progenitors were studied In vitro by erythrophagocytosis assay and by hematopoietic progenitor colony assay, respectively. Results. In an erythrophagocytosis assay using normal monocytes, RBC from nine FA patients showed increased binding index (defined as the percentage of monocytes with adherent or phagocytosed RBC) compared to that obtained with RBC from nine normal controls. Upon exposure to H2O2, the binding index of normal RBC increased, while that of FA RBC remained unchanged. In a set of different experiments, H2O2 treatment of peripheral blood mononuclear cells (PBMNC) caused a significant decrease of the number of colonies from circulating progenitor cells in all normal subjects; the inhibition was dose-dependent and direct as proven by using normal purified CD34+ cells. In nine FA patients colony assays from intact cells showed a decreased number of circulating progenitors as compared to normal subjects; however, H2O2 treatment of FA PBMNC did not cause any further decrease of the plating efficiency. Interpretation and Conclusions. Untreated FA cells behave as normal cells after exposure to the toxic effects of H2O2. However, since H2O2 exposure is inoffensive to circulating FA RBC and hematopoietic progenitors, it seems that a selection for cells resistant to further oxidative stress has taken place in the residual hematopoiesis of FA patients. We may surmise that the survival of cells that have suffered from oxidative damage may have increased the risk of their leukemic transformation.

Original languageEnglish
Pages (from-to)868-874
Number of pages7
JournalHaematologica
Volume83
Issue number10
Publication statusPublished - Oct 1998

Keywords

  • Fanconi's anemia
  • Hematopoietic progenitors
  • Oxidative stress

ASJC Scopus subject areas

  • Hematology

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