[EPO mediated proliferation and differentiation of human erythroid progenitor inhibited by FK228].

Aim: To investigate the function of histone deacetylases (HDACs) inhibitor FK228 in the EPO mediated proliferation and differentiation of human erythroid progenitor.

Methods: CD34(+) cells were separated from the granulocyte colony-stimulating factor-mobilized peripheral blood of patients with cancer. They were cultured for 7 days with serum-free medium containing stem cell factor (SCF), erythropoietin (EPO) or SCF+IL-3 in the presence of escalated dosages of FK228. After immunofluorescent staining with anti-GPA-PE and anti-CD36-FITC, cell count and Flow cytometric analysis were performed; CD34(+) cells were cultured for 7 days with serum-free medium containing SCF+IL-3 and enriched for CD36(+) GPA(-) cells, which were cultured for 7 days with serum-free medium containing EPO+FK228. Then the cell count was conducted. CD36(+) GPA(-) cells were cultured for 7 days with serum-free medium containing EPO in the presence or absence of FK228 and then they were stained with annexin V and PI.

Results: FK228 inhibited the generation of CD36(+) GPA(high), CD36(+) GPA(low) and CD36(+) GPA(-) cells in a dosage-dependent manner. FK228 induced the apoptosis of CD36(+) GPA(high) and CD36(+) GPA(low/-) cells in the presence of EPO.

Conclusion: FK228 can inhibit the EPO mediated proliferation and differentiation of human erythroid progenitor.