以阿糖胞苷为基础的化疗方案是AML的主要治疗模式，但个体间疗效差异显著，耐药复发严重影响预后，其影响因素和机制仍不清楚。我们前期研究发现核苷转运蛋白SLC29A1 rs3734703与AML患者诱导缓解率及远期生存密切相关。近期我们通过生物信息学、双荧光素酶报告基因试验发现miRNA-5194可以与rs3734703 A结合，据此我们推测：该位点变异影响了miRNA靶向调控SLC29A1，造成细胞内阿糖胞苷水平及敏感性不同，导致个体疗效差异。本课题拟在前期工作基础上，通过体内外试验及临床研究进一步明确SLC29A1表达下降可导致阿糖胞苷细胞毒作用减弱，证实rs3734703可作为AML患者接受阿糖胞苷为基础治疗的预后因子，探讨其通过miRNA调控靶基因表达和功能改变导致阿糖胞苷耐药的分子学机制。本研究以miRNA药物基因组学为切入点，为AML实施个体化治疗、改善预后提供了新的策略和依据。

The cytarabine(Ara-C)-based chemotherapeutic regimens have been the mainstay of treatment for all forms of AMLs in adult patients. However, there is wide interpatient variation in clinical response. Primary or acquired chemoresistance is the major therapeutic challenge faced in AML treatment with significant impact in long-term survival rates, and our understanding of these factors and mechanisms is still limited. In our previous study, we observed SLC29A1 rs3734703 significantly associated with CR and survival in AML patients who received Ara-C based treatment, which expected to be a prognostic factor for AML, but further studies on its exact relationship and mechanism with expression/activity of SLC29A1 are needed. Then by bioinformatics algorithms we found that rs3734703 is located near the miRNA-binding site, the preliminary results show that miRNA-5194 could bind to SLC29A1 when rs3734703 is the A allele. Therefore, we speculate that rs3734703 may affect the expression of SLC29A1 by miRNA-5194, may contribute to interindividual differences in tissue drug levels and response to Ara-C, resulting in different prognosis. Based on previous work, we intends to determine whether decreased expression of SLC29A1 can lead to weakened cytotoxicity of cytarabine, confirm rs3734703 genotypes may be associated with clinical outcomes of AML patients treated with ara-C based chemotherapy，and explore the potential mechanisms of which rs3734703 regulate target gene expression and functional lead to cytarabine resistance though miRNA. Taking miRNA pharmacogenomics as a new perspective, this study provides a new strategy for AML patients may potentially modulate leukemia response to conventional chemotherapy and improve outcomes based on individual genotypes.