p15 (INK4B) and E-cadherin CpG island methylation is frequent in Egyptian acute myeloid leukemia.

Background: Hypermethylation within the promoters of selected genes is an epigenetic pathway that appears to be especially common in all types of human haematopoeitic neoplasms. It is usually associated with inactivation of the involved genes, and can be reversed using demethylating agents. The aim of this study is to evaluate the frequency of p15 and E-cadherin promoter methylation in Egyptian acute myeloid leukemia (AML) patients in an attempt to identify a subset of patients who might be candidates for demethylating agents as a form of targeted therapy either as a primary or as an adjunct to current standard induction and post-remission regimens.

Material And Methods: In the present work we have studied tumor-associated aberrant p15 and E-cadherin promotor methylation in 59 newly diagnosed acute myeloid leukemia (AML) patients using methylation specific PCR.

Results: Aberrant p15 promoter methylation was detected in 49% (29/59) of the patients. In 4 of these patients, no DNA could be amplified by the p15 unmethylated reaction showing a complete methylation of both alleles in the examined region. In the remaining 25 cases both methylated and unmethylated DNA could be amplified. Aberrant methylation of E-cadherin was detected in 63% (37/59) of the cases. In all of these cases both the methylated and the unmethylated alleles were amplified denoting partial methylation of the examined region. Concomitant methylation of p15 and E-cadherin was detected in 40% (23/59) of all the cases tested, while in 27% (16/59) of the cases both genes were not methylated.

Conclusion: These results demonstrate that p15 and E-cadherin promoter methylation are frequent events in Egyptian AML and provide an impetus for larger studies to define the extent and pattern of methylation in the various subgroups of AML. Methylation studies, therefore, represent a novel additional tool to define the subset of patients who might benefit from demethylating agents,thus providing the molecular basis for targeted therapeutic approaches and better designing of risk-adapted therapy.