Histone deacetylase inhibitors represent a family of targeted anticancer 
compounds that are widely used against hematological malignancies. So far little 
is known about their effects on normal myelopoiesis. Therefore, in order to 
investigate the effect of histone deacetylase inhibitors on the myeloid 
commitment of hematopoietic stem/progenitor cells, we treated CD34(+) cells with 
valproic acid (VPA). Our results demonstrate that VPA treatment induces H4 
histone acetylation and hampers cell cycle progression in CD34(+) cells 
sustaining high levels of CD34 protein expression. In addition, our data show 
that VPA treatment promotes erythrocyte and megakaryocyte differentiation. In 
fact, we demonstrate that VPA treatment is able to induce the expression of 
growth factor-independent protein 1B (GFI1B) and of mixed-lineage leukemia 
translocated to chromosome 3 protein (MLLT3), which are crucial regulators of 
erythrocyte and megakaryocyte differentiation, and that the up-regulation of 
these genes is mediated by the histone hyperacetylation at their promoter sites. 
Finally, we show that GFI1B inhibition impairs erythroid and megakaryocyte 
differentiation induced by VPA, while MLLT3 silencing inhibits megakaryocyte 
commitment only. As a whole, our data suggest that VPA sustains the expression 
of stemness-related markers in hematopoietic stem/progenitor cells and is able 
to interfere with hematopoietic lineage commitment by enhancing erythrocyte and 
megakaryocyte differentiation and by inhibiting the granulocyte and 
mono-macrophage maturation.