[Methylation of P15INK4B gene in patients with myelodysplastic syndromes and demethylating effects of drugs].
OBJECTIVE
To detect the methylation of P15INK4B gene in patients with myelodysplastic syndromes (MDS) and to investigate the demethylating effects of decitabine and arsenic trioxide (As2O3).


METHODS
The bone marron mononuclear cells from 14 MDS patients were collected. The methylation of P15INK4B gene was detected with restrictive endonucleases combined with PCR technique. The peripheral blood mononuclear cells from one of the patients who had progressed into acute leukemia were treated with decitabine and As2O3 in vitro to test the change of methylation.


RESULTS
No methylation of P15INK4B gene was detected in MDS patients with low risk of leukemia. The methylation of P15K4B gene was found in 4 MDS patients with high-risk of leukemia and 4 patients who had progressed from MDS to acute leukemia. After exposed to decitabine or As2O3, the methylation went down by 50%.


CONCLUSIONS
P15INK4B gene hypermethylation is closely associated with MDS pathogenesis. Decitabine and As2O3 have demethylating effect on the cells from the MDS patient.
Ye
Xue-shi
XS
Department of Hematology, West China Hospital, Sichuan University, Chengdu 610041, China.
Liu
Ting
T
Cui
Xu
X
Meng
Wen-tong
WT
Xi
Ya-ming
YM
D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics*; D019175:DNA Methylation / Q000187:drug effects*; D000077209:Decitabine; D018450:Disease Progression; D020022:Genetic Predisposition to Disease; D006801:Humans; D007938:Leukemia / Q000235:genetics / Q000473:pathology; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000473:pathology; D010087:Oxides / Q000494:pharmacology*
D001152:Arsenicals; D050762:Cyclin-Dependent Kinase Inhibitor p15; D010087:Oxides; D000077209:Decitabine; D001374:Azacitidine; D000077237:Arsenic Trioxide