DNA Methylation in Promoter Region of P15 Gene in Patients of Acute Myeloid Leukaemia and Myelodysplastic Syndrome

Acute Myeloid Leukemia (AML) & Myelodysplastic syndrome (MDS) are hematological malignancies with ineffective hematopoiesis. Epigenetic modifications like DNA methylation and histone modifications are changes in DNA structure that do not involve sequence changes but are stably inherited. DNA methylation in promoter region results in transcriptional inactivation of tumor suppressor genes. Silencing of P15 gene can provide a selective advantage for tumors cells. Demethylating agents as anti-cancer drugs, have potential to revert the expression of P15 gene. Role of promoter methylation in p15 gene among AML & MDS and use of demethylating agents for treatment of AML & MDS are recent advances to be considered. Promoter Methylation in P15 gene in these malignancies varies worldwide due to environmental and ethnic variations. Due to paucity of Indian data and considering the therapeutic potential which methylation pattern offers, it is imperative to establish the methylation pattern among Indian patients. To study the DNA Methylation status in the promoter region of P15 gene in forty blood sample of AML & MDS cases and twenty five controls. DNA was extracted from forty one cases of AML & MDS patient's blood sample and controls. Extracted DNA was Bisulphite converted followed by MS-PCR. Amplified products were run on gel electrophoresis and analyzed under UV transilluminator. DNA methylation in promoter region of P15 gene in AML and MDS patients was found 72.7% and 62.5% respectively. In combined data analysis (AML+MDS) positivity was 70.7%, whilst all controls were negative. On statistical analysis study outcome were significant. Promoter P15 DNA methylation pattern in this study represent a novel additional tool to define the epigenetic subset in AML and MDS patients who might be benefitted from demethylating agents, thus providing the molecular basis for targeted therapeutic approaches, monitoring its efficacy and prognostication.