Abstract: The current work aims to detect the expression of DNA methyltransferase ( DNMTs ) mRNA in patients with myelodysplastic syndrome ( MDS ), to analyze the association between the expression of DNMTs and the status of pl5INK4B CpG land methylation, and to investigate the relationship between the expression of DNMTs and the clinical prognosis of patients with MDS. Methods: The mRNA expression of DNMT1, DNMT3A, and DNMT3B in 48 MDS patients and 20 normal subjects were determined using real-time reverse transcription polymerase chain reaction ( PCR ). The status of pl5 CpG land methylation in 48 MDS patients and 20 normal controls was measured by methylation-specific PCR. Results: There were no significant differences between the normal control group and the low-risk MDS patient group with three DNMT mRNA expression levels ( P > 0.05 ). However, the expression levels of the three DNMT mRNA were significantly higher in the high-risk MDS group than in the group with the low-risk MDS and the normal controls ( P < 0.01 ). The expression level of DNMT mRNA was positively correlated with the status of the pl5INK4B gene methylation. A total of 12 high-risk MDS patients received decitabine therapy, and 15 of the high-risk MDS patients also underwent IA/DA combination chemotherapy. There were no significant differences in the curative effects between the decitabine group and the IA/DA chemotherapy group ( P > 0.05 ). Conclusion: There is an abnormally high expression of DNMT mRNA in MDS patients, resulting in the hypermethylation inactivation of CpG island-associated tumor suppressor genes that are related to the cell cycle regulation. The overexpression of DNMT genes plays an important role in the low- to high-risk transition of MDS, and even in its progression to acute myeloid leukemia. The expression of DNMT mRNA can serve as a prognostic marker for MDS patients.