GNA15介导的脂肪酸氧化在急性白血病耐药及复发中的作用机制研究

批准号:
82000173
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
张加敏
依托单位:
学科分类:
白血病
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
张加敏
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中文摘要
成人急性白血病(acute leukemia, AL)总体预后差。耐药及复发是AL治疗失败的主要原因,进一步阐明其发生机制有重要的理论和临床意义。近年来,脂肪酸氧化(Fatty acid oxidation, FAO)等细胞能量代谢在白血病细胞耐药中的调控作用逐渐引起关注,但其调控机制尚不明确。我们前期研究发现,GNA15在AL初诊及复发患者中高表达,与耐药及复发相关,GNA15可能通过AMPK/STAT3通路调控AL细胞FAO过程,从而介导细胞耐药;既往研究提示FAO与白血病干细胞调控密切相关。基于此,课题组认为,GNA15介导的FAO可能在AL干细胞维持及耐药复发中起关键调控作用。本课题拟通过体内外研究,进一步探索GNA15对AL细胞FAO过程的具体调控机制,阐明GNA15信号介导的FAO在AL干细胞维持及耐药复发中作用,从而为AL耐药及复发的诊治提供新的理论依据和治疗靶点。
英文摘要
The overall prognosis of adult acute leukemia (AL) is poor. Drug resistance and relapse are the main reasons for the failure of AL treatment. In recent years, the role of cell energy metabolism such as Fatty acid oxidation (FAO) in drug resistance of leukemia has attracted increasing attention, but its regulatory mechanism is still unclear. Our previous study found that GNA15 was highly expressed in patients with de novo and relapsed AL, which was associated with drug resistance, relapse and poor prognosis. Metabolomic analysis indicated that GNA15 may mediate cell resistance by regulating FAO process, and previous studies suggested that FAO is involved in the regulation of leukemia stem cells. Based on this, we hypotheses that GNA15-mediated FAO may play a crucial role in the maintenance of leukemia stem cells, drug resistance and relapse. This project intends to further explore the specific regulatory mechanism of GNA15 on the FAO process of AL cells through in vivo and in vitro studies, and elucidate the role of FAO mediated by GNA15 in the maintenance of AL stem cells, drug resistance and relapse, so as to provide a new theoretical basis and therapeutic target for the diagnosis and treatment of AL resistance and relapse.
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DOI:doi.org/10.1186/s13062-023-00451-0
发表时间:2024
期刊:Biology Direct
影响因子:5.5
作者:Qiao Zhou;Jiamin Zhang;Jingsong Zhang;Simin Liang;Duo Cai;Han Xiao;Yu Zhu;Wenqiong Xiang;Fernando Rodrigues‐Lima;Jianxiang Chi;Fabien Guidez;Li Wang
通讯作者:Li Wang
国内基金
海外基金
