Effect of Arsenic Trioxide on Myelomonocytic Progenitor Cells in Patients with Myelodysplastic Syndrome in Vitro / 中国实验血液学杂志

ABSTRACT

The Effect of arsenic trioxide (As(2)O(3)) on myelomonocytic progenitor cells of patients with myelodysplastic syndrome was studied. Bone marrow CFU-GM was assayed in the agar semi-solid culture, and the bone marrow cells were incubated in liquid culture and the expressions of CD33, CD15 and bcl-2 on the marrow cells were detected by APAAP method in 24 patients. The suppressive effects of As(2)O(3) to CFU-GM were increased with the rise of As(2)O(3) concentrations. The suppression of As(2)O(3) (0.388 micro mol/L) to cluster formation was stronger than to colony formation, the suppressive rates were 70.78% vs 34.05% in low-risk group, and 86.76% vs 65.86% in high-risk group (P < 0.01), respectively. 0.194 micro mol/L of As(2)O(3) decreased clusters and increased colonies in low-risk group, but decreased clusters and did not change colonies in high-risk group. High concentration (1.94 micro mol/L) of As(2)O(3) downregulated the expression rate of CD33 and CD15 in both groups, and low concentration (0.194 micro mol/L) downregulated the expression rate of CD33 and upregulated the expression rate of CD15 in low-risk group, but decreased expression of CD33 and did not alter CD15 in high-risk group. At the same time, the high concentration of As(2)O(3) downregulated expression of bcl-2 and resulted in karyopyknosis and cytoplasm condensation; low concentration generated similar effect on expression of bcl-2 and cell morphology in high-risk group, but did not affect in low-risk. It is concluded that As(2)O(3) suppressed myelopoiesis and impelled myelomonocytic cells to apoptosis, low concentration of As(2)O(3) induced the proliferation and differentiation of myelomonocytic cells in low-risk group, however, suppressed the growth of myelomonocytic cells and accelerated the cells apoptosis in high-risk group.