Acute myeloid leukaemia: recent data on prognostic gene mutations, in relation to stratified therapies for elderly patients.

TET2 protein is encoded by the gene TET2 which specifically catalyses the demethylation of 5-methylcytosine to cytosine. Mutations in TET2 have been identified in a number of haematological malignancies, including leukaemias and lymphomas. In acute myeloid leukaemia (AML), loss of TET2 function drives DNA methylation and gene silencing, contributing to disease pathogenesis and progression, making it an interesting target. Although such mutations are considered rare, there is an increasing body in the literature identifying them as unfavourable prognostic markers in AML. The hypomethylating agent nucleoside analogue 5-azacytidine is used in the treatment of AML and other haematological malignancies i.e. myelodysplastic syndrome (MDS). It functions by re-activating silenced genes is responsible for cytosine methylation, thereby driving differentiation and also promoting apoptosis of dysfunctional haematological cells. The present review article deals with the consequences of DNA methylation in relation to TET2 in AML, focusing on the potential prognostic effect of TET2 gene mutations, along with demethylating epigenetic strategies towards prediction of therapeutic response. The necessity for personalized therapeutic regimes, especially for older patients suffering from AML with mutated TET2 and/or other genetic alterations, along with its prognostication are also underlined.