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Mutations of the epigenetic enzymes isocitrate dehydrogenase (IDH) 1 and 2, and the methylcytosine dioxygenase 'ten-eleven translocation 2' (TET2), are common in human myeloid malignancies and drivers of these disorders but the underlying mechanisms remain obscure. This review examines mutant IDH1/2 and TET2 enzymes in the context of responses to DNA damage and their potential involvement in age-related genomic instability. The clinical relevance of these findings and their potential application in novel therapeutic strategies is also discussed.

Roles of IDH1/2 and TET2 mutations in myeloid disorders