Hemimethylation of tumor supressor genes in leukemia patients

SANCHEZ DOVA, A.; GONZALEZ, L.N.; CARNERI, T.A.; CÁLCENA, E.N.; BOLZAN, A.D.; RICHARD, S.M.

Mar del Plata

Congreso; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2019

Sociedad Argentina de Investigación Clínica (SAIC)

Methylation and hemimethylation are important epigenetic modification related to the regulation of the genetic expression. In many types of cancer occur epigenetic aberrations, among which is the hypermethylation of tumor suppressor genes. DNA methylation increases, mainly in promoter genes regions, generates a reduction or transcription blockage in patients with different types of cancer. Hypermethylated tumor supresor genes are inactive. This could be a factor leading to the progress or malignancy of this disease. In this work we study the methylation profile of 3 tumor suppressor genes APAF-1, DBC-1 and ER in 30 patients with acute myeloid leukemia and chronic myeloid leukemia (16 AML and 14 CML) and in 30 controls samples by the methylationspecific PCR technique (MSP) with previous treatment of DNA with sodium bisulfite technique, for the conversion of unmethylated Cytosines into Uracil bases. We analyzed 22/30 patient samples and 25/30 controls. Significant correlations in patient methylation status (p?0.05) were found in APAF-1 and there is a tendency in DBC-1 gene?s promoters by Fisher?s test analysis. We found 41 % methylated samples in APAf-1 (5 % methylated + 36 % hemimethylated) and 78 % methylated in DBC-1 (39 % methylated + 39 % hemimethylated). ER % were no significative (data not shown). Finally, near 40 % of the patients analyzed, contain partial methylation in their promoters, which could mean a decrease in their expression. These results suggest that methylation in the promoters of the analyzed genes could be related to the events that generate the onset or progression of the disease. The silencing by hemimethylation in the promoter of the APAF-1 and DBC-1 genes, and the high percentage of methylation in both types of DBC-1, would lead to a decrease in its expression, which could generate effects that favor the process of leucemogenesis. We have to analyze deeply DBC and increase much more the number of samples to make these results more effective.