T-cell acute lymphoblastic leukaemia (T-ALL) is a rare aggressive haematological malignancy characterised by the clonal expansion of immature T-cell precursors. It accounts for 15% of paediatric and 25% of adult ALL. T-ALL is associated with the overexpression of major transcription factors (TLX1/3, TAL1, HOXA) that drive specific transcriptional programmes and constitute the molecular classifying subgroups of T-ALL. Although the dysregulation of transcription factor oncogenes is frequently associated with chromosomal translocations in T-ALL, epigenetic dysregulation resulting in changes to post-translational modifications of histones has also been reported. This includes non-coding intergenic mutations that form oncogenic neo-enhancers. This review will focus on the known epigenetically activating intergenic mutations reported in T-ALL, and will discuss the wider implications of neo-enhancer mutations in cancer.
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