Alterations Of MGMT, P15, TP53 And DNMT3A Genes In Acute Leukemias Patients

Izabela ZAWLIK, University of Rzeszow, Poland

1 Department of Genetics, Chair of Molecular Medicine, Faculty of Medicine, University of Rzeszow, Rzeszow, Poland
2 Laboratory of Molecular Biology, Center for Innovative Research in Medical and Natural Sciences, University of Rzeszow, Rzeszow, Poland
3 Department of Immunology, Chair of Molecular Medicine, Faculty of Medicine, University of Rzeszow, Rzeszow, Poland
4 Department of Chemotherapy, Cancer Center, Copernicus Memorial Hospital, Lodz, Poland

PURPOSE: Epigenetic changes play a significant role in development and progression of acute leukemia. Literature data indicate that especially important seems to be hypermethylation of p15 and MGMT genes. For the development and prognosis of acute leukemias is also important to evaluate mutation of DNMT3A and TP53 genes. The aim of the study was to determine whether the MGMT and p15 promoter hypermethylation and  DNMT3A and TP53 mutations have an impact on development acute leukemias.
METHODS: The clinical data of 55 patients diagnosed with AML or ALL between 1998 and 2003 were retrospectively analyzed. DNA was extracted from bone marrow of the patients with acute leukemia. The methylation status of MGMT was evaluated by methylation-specific PCR (MSP). Combined bisulfite restriction analysis (COBRA) was used to detect p15 methylation level. Mutation analysis of DNMT3A (R882H) was performed by PCR-RFLP method. Exons 5-8 of TP53 mutation was detected by sequencing.
RESULTS: We have found that p15 methylation and TP53 mutation was detected significantly more often in patients with AML than patients with ALL. Age at diagnosis was higher for patients with MGMT methylation. There were no significant relationships between type of leukemia and DNMT3A mutation and MGMT methylation. No significant differences were observed between age and survival in patients with or without DNMT3A and TP53 mutation and p15 methylation.
CONCLUSION: Epigenetic changes can be exploited in the clinics as biomarkers for acute leukemias.
FUNDING SOURCE: This study was supported by the grant of the National Science Center, Poland, no. 2011/01/B/NZ4/03345.