Aberrant p15 promotor methylation in acute leukaemia

ABSTRACT

The p15 gene is one of the tumour suppressorgenes located on chromosome 9p21. In acute leukemias alterations involving the p15 gene have been reported. Commonly, these alterations involve the c[p]g islands that are commonly aberrantly methylated and result in the transcriptional loss of this gene. To detect this aberrant methylation, we used methylation specific pcr which is a novel method of pcr that can rapidly assess the methylation status of virtually any c[p]g island. The study included 30 patients 17 cases of the novo all and 13 cases of de novo aml. Aberrant p15 gene mehylation was detected in 47.1% of cases of all and in 69.2% of casaes of AML. There was no statistically significant difference between methylated and unmethylated cases regarding the clinical and haematological data other than the peripheral blood blast cell count. On following up the patients to detect the response to therapy, there was a statistically significant difference in the response to therapy between methylated and unmethylated cases [p< 0.05]. Methylated case had a higher incidence of relapse or death [in all methylated cases 35.4% of the studied cases relapsed and 61.6% in aml patients] while the inidence of remission was 11.7% for all methylated cases and 7.7% for aml cases. Unmethylated all cases achieved remission in 41.2% of the studied group and unmethylated cases of AML reached remission in 61.6%. Aberrant p15 methylation may have important prognostic implications for clinical monitoing. And risk assessment. Also it opens new strategies of treatment using demethylating agents that can reverse this epigenetic change