Neo‐enhancers in T‐cell acute lymphoblastic Leukaemia (T‐ALL) and beyond

Abstract 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.