Long-range gene regulatory interactions in Acute Promyelocytic Leukaemia

急性早幼粒细胞白血病的长程基因调控相互作用

• 批准号: 1938329
• 金额: --
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1938329
• 关键词: Long; range; gene; regulatory; interactions

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.

急性早幼粒细胞白血病（APL）是一种急性白血病，其特征是涉及PML和RARA基因座的重排。APL是唯一敏感的靶向治疗纳入药理剂量的维甲酸，导致在大多数患者的良好的临床结果。尽管如此，大约20%的患者会复发，一部分患者会死于疾病进展。这种差异反应的潜在生物学原因尚不清楚，也不能通过突变谱或DNA甲基化状态来解释。我们假设，基因调控网络的差异可能会有所不同的反应性和难治性疾病的患者。我们的目标是使用Capture Hi-C来检测这两组患者的全基因组调控相互作用，以检测可能作为生物标志物的调控特征，从而预测对治疗的反应。这项研究可以确定对癌症进展至关重要的DNA元件，并可以突出可以特异性靶向治疗的信号通路。