造血发育中髓细胞转录调控的异常是造成髓系分化阻滞而导致急性髓细胞白血病（AML）发生的关键因素。近年来长链非编码RNA（lncRNA）在转录调控中承担的角色备受瞩目。本课题组前期应用高通量技术研究发现，AML的M3亚型的发生和治疗受到数个亚型特异性lncRNA的调控。这些前期发现提示lncRNA这一全新的转录调控元件可能活跃地参与AML各亚型的发生和治疗过程中。本课题组拟整合多层次高通量技术，结合生物信息学方法筛选与鉴定造血分化阻滞不同阶段AML各亚型特征性lncRNA，进一步通过分子生物学和动物模型深入研究这些lncRNA的转录调控模式和解析下游的转录调控网络，明确其在造血分化受阻中所发挥的作用。这一研究不仅有助于诠释lncRNA在造血系统髓系发育调控的功能，并对揭示白血病发生发展的分子机制及设计个体化治疗方案具有积极的理论价值。

The aberrant transcriptional regulation during hematopoiesis is considered as a critical factor of the pathogenesis of acute myeloid leukemia (AML). Emerging evidence has shown that long non-coding RNAs (lncRNAs), as a new player in the regulation of gene transcription, have been linked to the development of cancer, including leukemia. Our preliminary data has identified several lncRNAs involved in the development and treatment of acute promyelocytic leukemia (APL, AML-M3 subtype). These findings suggest that the identification of lncRNAs in AML is of help to understand the pathogenesis and treatment of leukemia. In this study, we plan to use high-throughput techniques and bioinformatic analysis to identify lncRNAs associated with specific AML subtypes blocked at the respective differentiation stages. Based on the identified lncRNAs, we will further apply molecular biology approaches and animal models to explore the regulatory mechanisms of these lncRNAs in AML development, investigate their downstream regulatory networks, and unravel their roles in blocking the differentiation of hematopoietic cells. This study will not only provide new insights into the important roles of lncRNAs in hematopoiesis, but also deepen our understanding of leukemogenesis and development of targeted therapies for individual patients.