DNA demethylation marks in chronic lymphocytic leukemia: it is time to let the cat out of the bag

In chronic lymphocytic leukemia (CLL), DNA methylation changes are essential in the pathogenesis of the disease and lead to the identification of potential biomarkers relevant for clinical follow-up and personalized medicine. Accordingly, understanding the mechanisms of controlling DNA methylation/demethylation is critical for future biomarker and therapeutic development in CLL.

The dynamic interplay between DNA methylation and DNA demethylation mechanisms in maintaining normal chromatin structure and gene expression in normal cells and the causes and consequences of an imbalance between the two processes are critical points highly discussed in recent years. The debate was recently reinforced by the description of an active DNA demethylation pathway by which 5-methylcytosine (5-mCyt) is sequentially converted to 5-hydroxymethylcytosine (5-hmCyt) and, in a less efficient fashion, to 5-formylcytosine and 5-carboxylcytosine by TET dioxygenases.

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