白血病是中国居民死亡的十大恶性肿瘤之一，在35岁以下人群及儿童中占首位。MLL转位是造成婴幼儿白血病的主要原因，发生率约为70%～80%。我们前期大量的工作表明：临床上最常见的几个MLL转位伴侣，包括AFF1和AFF4，共处于一个蛋白质复合物，命名为超级转录延伸复合物（Super Elongation Complex，SEC）。AFF1和AFF4是同源蛋白，可分别形成SEC。AFF4-SEC通过调控启动子近段Pol II暂停释放，在机体应激反应及早期胚胎发育及婴幼儿白血病发生发展中发挥着重要作用。然而，AFF1-SEC在转录调控中的具体作用机制尚不清楚。本项目将利用相分离分析及组学二代测序及遗传学手段，系统性阐明AFF1-SEC和AFF4-SEC在转录延伸调控中的特异性调控机理，及在小鼠发育中的作用。对SEC功能的系统性研究将极大促进我们对婴幼儿白血病及SEC相关临床疾病致病机理的理解。

Leukemia is one of the leading causes of death in China, especially in children and adults under age 35. MLL translocation is the main cause of infant leukemia with frequency up to 70~80%. Previously, we have shown that many of the most common MLL fusion partners, including AFF1 and AFF4, forms the same complex, named Super Elongation Complex (SEC). AFF1 and AFF4 are paralogues, and the scafold proteins of SEC. AFF4-SEC plays essential roles in rapid transcriptional activation upon stress, early embryonic development and also infant leukemia through regulating transcriptional pause release. However, it is still unclear the exact function of AFF1-SEC in transcriptional control. Here, we will apply most advanced phase separation, next generation sequencing, and genetic techniques, to systematically demonstrate the roles of AFF1 in transcription control, and the molecular signaling underlying how the misregulation of AFF1 leads to developmental defects. The research on the physiological function of AFF1 will greatly enhance our understanding on the pathogenesis of infant leukemia and also AFF1-related human diseases.