Genistein Protects Hematopoietic Stem Cells against G-CSF-Induced DNA Damage
Menée sur un modèle murin, cette étude montre que la génistéine, une isoflavone, peut protéger les cellules souches hématopoïétiques contre les dommages causés à l'ADN par le facteur G-CSF utilisé dans le traitement des neutropénies
Granulocyte colony-stimulating factor (G-CSF) has been utilized to treat neutropenia in various clinical settings. Although clearly beneficial, there are concerns that the chronic use of G-CSF in certain conditions increases the risk of myelodysplastic syndrome (MDS) and/or acute myeloid leukemia (AML). The most striking example is in severe congenital neutropenia (SCN). SCN patients develop MDS/AML at a high rate that is directly correlated to the cumulative lifetime dosage of G-CSF. MDS and AML that arise in these settings are commonly associated with chromosomal deletions. We have demonstrated in this study that chronic G-CSF treatment in mice results in expansion of the hematopoietic stem cell population. In addition, primitive hematopoietic progenitors from G-CSF-treated mice show evidence of DNA damage as demonstrated by an increase in double strand breaks and recurrent chromosomal deletions. Concurrent treatment with genistein, a natural soy isoflavone, limits DNA damage in this population. The protective effect of genistein appears to be related to its preferential inhibition of G-CSF-induced proliferation of hematopoietic stem cells. Importantly, genistein does not impair G-CSF-induced proliferation of committed hematopoietic progenitors, nor diminish neutrophil production. The protective effect of genistein was accomplished with plasma levels that are attainable through dietary supplementation.