Long-range gene regulatory interactions in Acute Promyelocytic Leukaemia

急性早幼粒细胞白血病（APL）是一种以PML和RARA基因座重排为特征的急性白血病。APL对结合视黄酸药物剂量的靶向治疗具有独特的敏感性，对大多数患者产生了良好的临床结果。尽管如此，大约20%的患者会复发，一部分患者会因病情进展而死亡。这种差异反应的潜在生物学原因尚不清楚，也不能用突变谱或DNA甲基化状态来解释。我们假设基因调控网络的差异可能在反应性和难治性疾病患者之间有所不同。我们的目标是使用Capture Hi-C来表征这两组患者的全基因组调节相互作用，以表征可能作为生物标志物来预测治疗反应的调节特征。这项研究可能identiö' DNA元素对癌症进展至关重要，并可能突出可以特异性靶向治疗的信号通路。

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.