Long-range gene regulatory interactions in Acute Promyelocytic Leukaemia

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Acute Promyelocytic Leukaemia (APL) is an acute leukaemia characterised by rearrangements involving the PML and RARA loci. APL is uniquely sensitive to targeted therapy incorporating pharmacological doses of retinoic acid, resulting in excellent clinical outcomes for most patients. Despite this, approximately 20% of patients will relapse and a proportion will die fnm progressive disease. The underlying biological reasons for this differential response remain unclear and are not explained by mutational profile or DNA methylation status. We hypothesise that differences in gene regulatory networks may differ between patients with responsive and refractory disease. We aim to use Capture Hi-C to characterise genome-wide regulatory interactions in these two groups of patients to characterise a regulation signature that may act as biomarkers to predict response to therapy. This study may identiö' DNA elements that are crucial to cancer progression and could highlight signalling pathways that can be specifically targeted therapeutically.