转录因子CEBPE调控不同亚型AML细胞分化机制及靶向治疗研究

批准号:
32000497
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
杜玉昕
依托单位:
学科分类:
细胞命运及重编程
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
杜玉昕
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中文摘要
急性髓系白血病(AML)是一种高度异质性恶性血液疾病,患者总体预后较差,亟需寻找新的潜在分子靶标及靶向药物。申请人前期研究发现转录因子CEBPE表达是不同亚型AML的独立预后因子,CEBPE高表达的患者预后更好。我们预实验结果发现,CEBPE在调控AML细胞分化方面发挥着不可或缺的作用。因此,本项目拟从不同亚型AML临床样本、细胞和动物模型三个层面阐述CEBPE对各亚型AML细胞分化的影响;结合ChIP-Seq及RNA-Seq技术,筛选CEBPE直接调控的靶基因,生物信息学方法分析其在AML细胞分化中的关键分子途径;采用药物重定位方法,识别靶向CEBPE的潜在药物,进而探索适用于不同亚型AML的治疗策略。本项目将为各亚型AML患者的分子靶向治疗提供新的思路。
英文摘要
Acute myeloid leukemia (AML) is the most common type of acute hematopoietic malignancy in adults, characterized by a highly heterogeneous and poor overall prognosis. It is urgent to identify novel molecular targets for improvement of therapy. Our previous research found granulocyte-specific transcription factor CEBPE expression was an independent prognostic factor in patients with different subtypes of AML. High-expression of CEBPE was found to be associated with the better prognosis of AML. Pre-experiments of this project shows that CEBPE plays an indispensible role in regulating the acute promyelocytic leukemia (APL) cell differentiation. Therefore, in this study, we would explain the impact of CEBPE on the cell differentiation of AML through three levels of clinical specimens, cells and animal models. In combination with ChIP-Seq and RNA-Seq, the target genes directly regulated by CEBPE will be screened, and their key biological pathways in AML will be enriched and analyzed by bioinformatics approach. In addition, combined with drug repositioning strategy, the potential drugs for different subtypes of AML will be identified by targeting the gene set directly regulated by CEBPE. This project aims to explore the regulatory mechanism of transcription factor CEBPE on the differentiation of different subtypes of AML cells, and further explore its targeted treatment strategy, which is expected to provide novel ideas for molecular targeted treatment of AML patients.
期刊论文列表
专著列表
科研奖励列表
会议论文列表
专利列表
DOI:10.1016/j.gendis.2022.05.020
发表时间:2023-11
期刊:GENES & DISEASES
影响因子:6.8
作者:Lv, Yan;Ma, Xiao;Ma, Yuxin;Du, Yuxin;Feng, Jifeng
通讯作者:Feng, Jifeng
Single-cell analysis reveals the chemotherapy-induced cellular reprogramming and novel therapeutic targets in relapsed/refractory acute myeloid leukemia.
单细胞分析揭示化疗诱导的细胞重编程和复发/难治性急性髓系白血病的新治疗靶点
DOI:10.1038/s41375-022-01789-6
发表时间:2023-02
期刊:LEUKEMIA
影响因子:11.4
作者:Li, Kening;Du, Yuxin;Cai, Yun;Liu, Wenjie;Lv, Yan;Huang, Bin;Zhang, Lishen;Wang, Zhi;Liu, Ping;Sun, Qian;Li, Ning;Zhu, Mengyan;Bosco, Bakwatanisa;Li, Liangyu;Wu, Wei;Wu, Lingxiang;Li, Jianyong;Wang, Qianghu;Hong, Ming;Qian, Sixuan
通讯作者:Qian, Sixuan
Single-cell RNA sequencing unveils the communications between malignant T and myeloid cells contributing to tumor growth and immunosuppression in cutaneous T-cell lymphoma
单细胞 RNA 测序揭示恶性 T 细胞和骨髓细胞之间的通讯,促进皮肤 T 细胞淋巴瘤的肿瘤生长和免疫抑制
DOI:10.1016/j.canlet.2022.215972
发表时间:2022-10-20
期刊:CANCER LETTERS
影响因子:9.7
作者:Du, Yuxin;Cai, Yun;Feng, Jifeng
通讯作者:Feng, Jifeng
DOI:10.1186/s12964-022-01031-x
发表时间:2023-01-23
期刊:CELL COMMUNICATION AND SIGNALING
影响因子:8.4
作者:Lv, Yan;Du, Yuxin;Li, Kening;Ma, Xiao;Wang, Juan;Du, Tongde;Ma, Yuxin;Teng, Yue;Tang, Weiyan;Ma, Rong;Wu, Jianqiu;Wu, Jianzhong;Feng, Jifeng
通讯作者:Feng, Jifeng
国内基金
海外基金
