MLL-AF4 Spreading Identifies Binding Sites that Are Distinct from Super-Enhancers and that Govern Sensitivity to DOT1L Inhibition in Leukemia

Jon Kerry et al have probed gene regulation in mixed-lineage leukemia (MLL), highlighting a possible biomarker for treatment selection and combination. MLL is a form of leukemia characterised by the translocation of the MLL gene from chromosome 11. This translocation produces over 120 fusion proteins – the most common being MLL-AF4. The team investigated MLL-AF4 binding to gene targets. They found that rather than just binding to the promoter sequence of target genes, MLL-AF4 also binds to the gene body – so call MLL-AF4 spreading, a new concept they have introduced in this paper. This spreading is associated with high transcription of genes involved in driving cancergenesis, opening an opportunity for this process to act as a biomarker for therapeutic response. 

The research was published in the journal Cell Reports on 10 January 2017.