Wang Xiaokang, Tong Yong, Xun Tianrong, Feng Haixing, Lei Yuhe, Li Yuanqing, Wu Kit Hang, Qiu Fang
Department of Pharmacy, Shenzhen Longhua District Central Hospital, Shenzhen 518110, China.
Department of Pharmacy, Shenzhen Hospital, Southern Medical University, Shenzhen 518000, China.
Fundam Res. 2023 May 16;5(4):1781-1794. doi: 10.1016/j.fmre.2023.04.012. eCollection 2025 Jul.
Acute myeloid leukaemia (AML) is a malignant disease of myeloid hematopoietic stem/progenitor cells. Despite improved understanding of the pathogenesis of AML since the 1980s, the standard treatment for AML has remained virtually unchanged. Numerous studies have found poor survival rates and high relapse rates among older patients with AML. Several novel therapies for AML, including cytotoxic drugs, genetically- and epigenetically-targeted drugs, and immunotherapies, have been developed in recent years. Alternative treatments with improved efficacy are required for AML because many patients cannot tolerate the toxic effects of chemotherapy. Non-coding RNAs, including microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), are attractive treatment targets for cancers and several other diseases. LncRNAs, miRNAs and circRNAs regulate DNA transcription and translation. Over the past decade, significant efforts have been made to develop RNA-based therapies, mainly antisense oligonucleotides and small interfering RNA, some of which have been approved for clinical use. Here we reviewed the mechanisms underlying the and effects of promising targets and potential drugs, focusing on the drugs most likely to be used for clinical treatment, to aid in the development of precision therapy for AML.
急性髓系白血病(AML)是一种髓系造血干细胞/祖细胞的恶性疾病。尽管自20世纪80年代以来对AML发病机制的认识有所提高,但AML的标准治疗方法几乎没有改变。许多研究发现老年AML患者的生存率低且复发率高。近年来已开发出几种针对AML的新型疗法,包括细胞毒性药物、基因和表观遗传靶向药物以及免疫疗法。由于许多患者无法耐受化疗的毒性作用,因此需要疗效更好的替代治疗方法来治疗AML。非编码RNA,包括微小RNA(miRNA)、长链非编码RNA(lncRNA)和环状RNA(circRNA),是癌症和其他几种疾病有吸引力的治疗靶点。LncRNA、miRNA和circRNA调节DNA转录和翻译。在过去十年中,人们为开发基于RNA的疗法做出了巨大努力,主要是反义寡核苷酸和小干扰RNA,其中一些已被批准用于临床。在此,我们综述了有前景的靶点和潜在药物的作用机制及效应,重点关注最有可能用于临床治疗的药物,以助力AML精准治疗的发展。