靶向急性髓系白血病特定基因亚型的治疗研究进展

Advances in the Treatment of Targeting Specific Gene Subtypes of Acute Myeloid Leukemia

关键词:  急性髓系白血病  基因突变  基因融合  临床治疗  新兴药物

Key words:  acute myeloid leukemia  gene mutations  gene fusion  clinical treatment  novel drugs

摘要:

急性髓系白血病（acute myeloid leukemia，AML）是一类在发病机制及临床表现方面均呈现多样化的异质性疾病。研究表明AML涉及多种基因融合和突变，主要包括一些编码转录因子的基因融合（如PML-RARA和RUNX1-RUNX1T1）的融合、关键信号分子（如NPM1和FLT3）及表观遗传修饰子（如IDH1和IDH2）的突变。AML中这些基因组学的改变通常与患者的临床诊断及预后有明确的相关性，广泛用于指导AML临床用药及指示预后。然而AML患者中不断发现新的基因突变且较多患者缺乏已知生物标记物，阐明AML中基因亚型的功能性将有助于治疗药物的研发。本文综述了AML中一些基因分型的功能性、主要临床治疗方法及靶向AML特定基因亚型的药物治疗进展，以期为新的AML基因亚型的治疗药物研发提供参考依据。

Abstract:

Acute myeloid leukemia(AML) is a heterogeneous disease characterized by diversity in molecular pathogenesis and clinical manifestations. Studies have shown that AML involves multiple gene fusion and mutations, including gene fusion of transcription factors(such as PML-RARA and RUNX1-RUNX1T1), mutations of key signaling molecules(such as NPM1 and FLT3) and epigenetic modifiers(such as IDH1 and IDH2). These genomics changes in AML usually have clear correlation with the clinical diagnosis and prognosis of the patients, which are widely used to guide the clinical treatment and indicate the prognosis of AML. However, there are still many AML patients lacking known biomarkers, and some new genetic mutations are constantly emerging. Elucidating the functionality of gene subtypes in AML will contribute to the development of therapeutic drugs. This article elaborate on some known functional genotyping in AML, the current clinical treatment of AML, and review the progress of drug therapy targeting specific AML subtypes. It is expected to provide a new reference for the development of therapeutic drugs for new AML gene subtypes.