Supporting data for "Long Noncoding Transcriptome in Acute Myeloid Leukaemia"

The landscape of transcribed super-enhancers (SEs) in acute myeloid leukemia (AML) has not been characterized. Established methods for determination of SE landscape rely on chromatin immunoprecipitation of H3K27ac and H3K4me1 followed by sequencing to ascertain chromatin pattern. Enhancer RNA expression represents an independent method to measure functional enhancer activities. Recent strategies focusing on pre-defined enhancer elements have enabled the determination of SE landscape in large cohorts of primary tumor samples using RNA-sequencing. In this study, we performed deep total RNA-sequencing to study the landscape of transcribed SE loci in 185 AML patients and observed transcribed SE activities being closely associated with subtype-specific transcriptional programs in AML, revealing the pervasiveness of SE-associated deregulation of coding genes. Our findings suggest transcribed SE loci are pervasively involved in leukemogenic pathways, with clinical utility as biomarkers for prediction of treatment response.

急性髓系白血病（acute myeloid leukemia, AML）中，转录活性超级增强子（transcribed super-enhancers, SEs）的调控全景尚未被系统表征。当前用于绘制超级增强子调控图谱的经典方法，依赖于针对组蛋白H3K27ac与H3K4me1的染色质免疫共沉淀，结合测序技术以明确染色质调控模式。增强子RNA（enhancer RNA）的表达水平是衡量功能性增强子活性的独立检测手段。近期聚焦于预定义增强子元件的研究策略，已实现通过RNA测序（RNA-sequencing）对大型原代肿瘤样本队列中的超级增强子调控图谱进行绘制。本研究通过深度全转录组RNA测序，对185例急性髓系白血病患者体内的转录活性超级增强子位点全景展开分析，发现转录活性超级增强子的活性与AML的亚型特异性转录程序紧密关联，揭示了编码基因受超级增强子调控失调的普遍性。本研究结果表明，转录活性超级增强子位点广泛参与致白血病通路，可作为预测治疗应答的生物标志物，具备临床应用价值。