阿糖胞苷联合蒽环类药物治疗是急性髓系白血病（AML）标准化疗方案，但患者的疗效和和预后不一，遗传因素是AML药物反应及预后差异的主要原因之一。本项目前期研究发现lncRNA GAS5 rs55829688多态性与AML患者生存期相关，其功能可能与影响TP63对GAS5启动子的调节从而升高其表达有关。由于GAS5可抑制糖皮质激素受体的功能，糖皮质激素具有促进造血的作用，而骨髓抑制是AML的主要死因，本研究拟通过临床研究结合细胞实验，查明GAS5 rs55829688多态性影响AML的预后是否与其影响联合化疗后骨髓抑制的恢复有关；并通过分离培养人脐带血造血干细胞（HSCs），在阿糖胞苷诱导损伤的HSCs细胞模型，通过干预GAS5表达和质谱分析，查明GAS5在HSCs造血中的作用及其分子机制。本项目旨在探讨GAS5影响AML预后的机制，为促进AML的个体化治疗和骨髓抑制的恢复提供新的思路。

cytosine arabinoside (Ara-c) combined with anthracycline-based chemotherapy is the standard chemotherapy treatment for acute-myeloid leukemia (AML). However, both chemosensitivity and prognosis AML patients show remarkable individual differences. Genetic factors are acknowledged to be one of the main causes for this individual differences. Our previous study have observed that the long non-conding RNA GAS5 promoter single nucleotide polymorphism rs55829688 was significantly associated with AML prognosis as indicated by overall survival (OS). Moreover, this polymorphism could alter the promoter activity and the expression of GAS5 through intervening the action of transcript factor TP63. Study has shown that GAS5 can interfere with the actions glucocorticoids (GCs) through binding activated GC receptors, and in consideration of the important role of GCs in stimulating bone marrow hematopoiesis, while myelosupression is the most important cause of death in AML patients during chemotherapy, this program is designed to make clear the influence of GAS5 rs55829688 polymorphism on AML prognosis is related to inhibition in recovery of myelosupression after chemotherapy by both clinical and cellular studies. By isolating and culture of hemopoietic stem cell (HSCs) from human umbilical cord blood and using Ara-c induced HSCs damage, through interfering with GAS5 expression by overexpression and siRNA, to explore the role of GAS5 in hematopoiesis under Ara-c exposure and the possible mechanisms.