急性髓细胞性白血病（acute myeloid cell leukemia，AML）是一类造血细胞分化受阻、细胞无序增殖的恶性血液肿瘤。DNA损伤应答（DDR）通路失常是促进AML进程的重要因素之一。孤儿snoRNA（orphan snoRNA）是一类目前发现可富集在染色质区的非编码RNA分子。我们前期筛选鉴定了一批和染色质相关的孤儿 snoRNA，其中发现 SNORA73 与AML细胞DNA损伤修复有关，本项目拟在前期发现基础上开展下列研究：（1）在临床样品及小鼠模型中阐明SNORA73的功能及其与AML的关系；（2）研究SNORA73与DDR蛋白PARP1的互作机制；（3）阐明SNORA73调控AML DNA损伤积累和疾病进程的分子机制。本项目完成，不仅揭示孤儿snoRNA新功能，阐明其在AML发生发展中的作用机制，还为临床治疗提供潜在分子靶标和联合治疗策略提供理论依据。

Acute myeloid leukemia(AML) is an aggressive hematologic malignancy which originates from uncontrolled expansion of immature blood cells with the blockage of differentiation. Dysregulation of DNA damage response（DDR）can facilitate AML progression. Orphan snoRNA is a kind of non-coding RNAs which can be enriched in chromatin. We previously found that a mass of orphan snoRNAs are highly enriched in the chromatin-bound fraction，suggesting their potential function in chromatin dynamics including DDR. We found that an orphan snoRNA SNORA73 could influence DNA damage response in AML cells. Based on the previous findings, the project proposed following studies: (1) illuminate the functions of SNORA73 in both AML DDR and AML progression in clinical samples and in vivo; (2) the precise interaction mechanism of the SNORA73-PARP1 complex and the role of SNORA73 in PARP1 regulation ;(3) the mechanism of SNORA73 to regulate DNA damage accumulation and disease progression in AML. The project would propose a new insight of orphan snoRNA fuction and may provide a potential therapeutic target and the theoretical basis for drug combination for AML treatment.