Hypermethylierung von E-Cadherin und HIC-1 bei zwei prognostisch verschiedenen AML-Subgruppen

In this essay the amount of methylation of two different zytogenetic types of acute myeloid leukemia (AML) was compared. The DNA of 7 patients with t(8;21), who were part of the low-risk group and 8 patients with monosomy 5 or 7 or del(5q) or del(7q), who were part of the high-risk group an had a low life expectancy, as well as the DNA of 8 patients, who did not suffer from a malignant disease, was analysed. The aim of this analysis was to find out if certain AML-divergent subgroups differed from each other concerning methylation-frequency or methylation phaenotype. A semiquantitative assessment of the amount of methylation by means of PCR-product-sequencing according to Melki. et al. was not suitable for this purpose, which meant that a significantly more labour- and cost-intensive methode (cloning and automatic-sequencing) had to be carried out. All AML patients turned out to have a significantly higher methylation-frequency than the patients not suffering from a malignant disease, which shows that methylation can be seen as an epigenetic alteration, which is relevant in the development of AML. By contrast, an analysis of the cytogenetic subgroup showed no difference with regard to topography and frequency of methylated CpG-dinucleotides. On the bases of two promotor-regions (E-Cadherin and HIC-1) it can be concluded that abberant methylation is a frequent side-effect with AML-patients. It does however not show a preference for certain cytogenetic risk constellations. Further tests in this field would be required to assess the pathogenetic importance of promotor-methylation for AML and, based on that, find therapeutic substances, e.g. demethylation-agence for treatment of progressive leukemia.