OBJECTIVETo investigate the biological changes in myelodysplastic syndromes (MDS) myeloid blast cell line MDS-L after different duration and concentration of As2O3/TRAIL (TNF related apoptosis inducing ligand) treatment.

METHODSMDS-L cells were treated with As2O3 and TRAIL at 9 different concentrations and the treated cells were detected at 24 h, 48 h and 72 h for biologic indexes. The same detections were conducted in untreated MDS-L cells and normal and MDS marrow cells as controls. Apoptosis was assayed by flow cytometry after Annexin V-FITC labelling. Differentiation-induction effect of these drugs on the cells were detected by morphologic examination and CD34(+) proportion analysis after 24 hours treatment and further agar culture for 18 days; P15(ink4b) mRNA expression were detected by RT-PCR and its protein expression by DAB immunocytochemistry, P15(ink4b) DNA methylation by methylation specific PCR (Msp).

RESULTSAs2O3/TRAIL treatment promoted MDS-L cells to undergo apoptosis and As2O3 plus TRAIL showed obvious differentiation-induction effect on MDS-L. P15(ink4b) mRNA expression was upregulated in MDS-L cell line after different drug treatment but almost no protein expression increased. Increased P15 expression seemed to be related with DNA demethylation effect of these drugs.

CONCLUSIONSAs2O3 or/and TRAIL treatment could promote apoptosis of the clonal cells and induce incomplete cell differentiation. The drugs treatment could also increase P15(ink4b) expression in MDS-L cell line through their demethylation effects.