Deletion Of P15 Gene And Promoter Methylation In Myelodysplastic Syndromes

Background: Myelodysplastic syndrome (MDS) is a clonal disorder of hematopoietic stem cells, characterized by ineffective hematopoiesis of bone marrow, peripheral blood cytopenia and susceptibility to acute myeloid leukemia (AML). The pathogenesis of MDS remains poorly understood, and there were also no definite molecular markers in most MDS. According to molecular biological study of cancers, a series of genetic or epigenetic alteration, especially the activation of oncogenes and the inhibition of tumor-suppressor genes have major contributions to the development of many human malignant tumors. Methylation of DNA is different from mutation and absence, because it doesn't alter the DNA sequence. Therefore, methylation of DNA is a reversible change, and this will be a new target of therapy.Objective: To examine the mRNA expression levels of p15 gene and the methylation status of its promoter region in myelodysplastic syndromes (MDS), and to explore the correlation between p15 gene methylation and pathogenesis, development of MDS. Method: Mono-nucleus cell are extracted from bone marrow of 32 cases with MDS. Methylation specific polymerase chain reaction (MS-PCR) was used to examine the methylation status of p15 gene promoter region in the bone marrow of 32 patients with MDS, and reverse transcription polymerase chain reaction (RT-PCR) was used to detect the mRNA expression levels of p15 gene.Results: 14 cases were found to have an increased methylation in the promoter region, especially in patients with high risk MDS. But this could not exist in the nonmalignant hematological diseases. There was a significantly difference between the two groups (P<0.05). P15 mRNA level was significantly decreased in patients with MDS. There existed a significant correlation between p15 methylation and mRNA decrease. P15 gene was expressed in all of the nonmalignant hematological diseases, but only 10 cases in patients suffered MDS had the expression of p15 mRNA. Part of the samples which had no expression of p15 gene mRNA were found the aberrant DNA methylation of p15 gene promoter region, while there were no aberrant DNA methylation in the samples which expressed p15 gene mRNA.Conclusion: Our study suggests that hypermethylation of the p15 gene promoter region may contribute to the loss of expression of p15 gene mRNA in MDS. Aberrant DNA methylation in promoter region of p15 gene is associated with the pathogenesis and prognosis of MDS.