FANCONIS ANEMIA CELLS ARE RELATIVELY RESISTANT TO H2O2-INDUCED DAMAGE

Background and Objective. Fanconi's anemia (FA) is a rare autosomal re cessive syndrome characterized by skeletal abnormalities, late onset b one marrow failure and susceptibility to neoplasias. Reduced defense a gainst oxidative stress is thought to be one of the cell damaging mech anisms. We investigated In vitro the effects of oxidative stress on re d blood cells (RBC) and on hematopoietic progenitor growth of normal d onors and of FA patients. Design and Methods. The effects of hydrogen peroxide (H2O2) on RBC and hematopoietic progenitors were studied in v itro by erythrophagocytosis assay and by hematopoietic progenitor colo ny 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 phagocy tosed RBC) compared to that obtained with RBC from nine normal control s. Upon exposure to H2O2, the binding index of normal RBC increased, w hile that of FA RBC remained unchanged. In a set of different experime nts, H2O2 treatment of peripheral blood mononuclear cells (PBMNC) caus ed a significant decrease of the number of colonies from circulating p rogenitor cells in all normal subjects; the inhibition was dose-depend ent and direct as proven by using normal purified CD34(+) cells. In ni ne FA patients colony assays from intact cells showed a decreased numb er 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. H owever, since H2O2 exposure is inoffensive to circulating FA RBC and h ematopoietic progenitors, it seems that a selection for cells resistan t to further oxidative stress has taken place In the residual hematopo iesis of FA patients. We may surmise that the survival of cells that h ave suffered from oxidative damage may have increased the risk of thei r leukemic transformation. (C) 1998, Ferrata Storti Foundation.