[Biologic changes in MDS-L cell line induced by As2O3 and/or TRAIL].
OBJECTIVE
To 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.


METHODS
MDS-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).


RESULTS
As2O3/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.


CONCLUSIONS
As2O3 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.
Li
Xiao
X
Department of Hematology, the Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200233, China.
Pu
Quan
Q
Shen
Wei-ming
WM
Tohyama
K
K
Deeg
H J
HJ
D018952:Antigens, CD34 / Q000032:analysis; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010087:Oxides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*; D013997:Time Factors
D018952:Antigens, CD34; D001152:Arsenicals; D050762:Cyclin-Dependent Kinase Inhibitor p15; D010087:Oxides; D012333:RNA, Messenger; D053221:TNF-Related Apoptosis-Inducing Ligand; D000077237:Arsenic Trioxide