[Epigenetic regulatory mechanisms and their disorders in leukemia]

The term epigenetics includes regulatory mechanisms that influence gene expression without any changes in the sequence of the DNA, namely DNA methylation, histone modification and small, non-coding RNAs. Methylation of the DNA leads to the repression of gene expression, while histone modification can result in both activation and inhibition of the transcription depending on the type and site of modification. These mechanisms are confirmed to have important pathogenetic role during the process of leukemogenesis. In distinct subtypes of leukemia specific alterations of the DNA methylation profile, histone code and typical changes of the microRNA expression levels have been observed. The importance of them is inhered in their promising potential clinical applications. In order to achieve further improvement in the therapeutic results of leukemia, prognostic classification has to be further improved. With the help of the epigenetic alterations, subgroups could be differentiated within the known prognostic groups. Changes in the DNA methylation pattern, histone code and microRNA expression levels correlate with the success of the treatment in many cases, moreover they could provide help to predict chemoresistance or detect the minimal residual disease following chemotherapy. Enzymes influencing the structure of chromatin form a wide variety of new potential therapeutic targets. Based on preliminary results, sorts of epigenetic therapy may be combined successfully either with each other or with conventional chemotherapeutic drugs in the treatment of leukemia.