Wang Yuhui, Wu Nan, Liu Duo, Jin Yan
Laboratory of Medical Genetics, Harbin Medical University, Harbin, Heilongjiang, P.R. China.
Department of Pharmacy, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, P.R. China.
Curr Genomics. 2017 Oct;18(5):378-384. doi: 10.2174/1389202918666170329110349.
Since the first fusion gene was discovered decades ago, a considerable number of fusion genes have been detected in leukemia. The majority of them are generated through chromosomal rearrangement or abnormal transcription. With the development of techniques, high-throughput sequencing method makes it possible to detect fusion genes systematically in multiple human cancers. Owing to their biological significance and tumor-specific expression, some of the fusion genes are attractive diagnostic tools and therapeutic targets. Tyrosine kinase inhibitors (TKI) targeting BCR-ABL1 fusions have been widely used to treat CML. The combination of ATRA and ATO targeting PML-RARA fusions has proven to be effective in acute promyelocytic leukemia (APL). Moreover, therapy with high dose cytarabine (HDAC) has significantly improved the prognosis of core binding factor (CBF) acute myeloid leukemia (AML) patients. Therefore, studies on fusion genes may benefit patients with leukemia by providing more diagnostic markers and therapies in the future.
The presented review focuses on the history of fusion genes, mechanisms of formation, and treatments against specific fusion genes in leukemia.
自数十年前发现首个融合基因以来,白血病中已检测到相当数量的融合基因。其中大多数是通过染色体重排或异常转录产生的。随着技术的发展,高通量测序方法使得在多种人类癌症中系统地检测融合基因成为可能。由于其生物学意义和肿瘤特异性表达,一些融合基因是有吸引力的诊断工具和治疗靶点。靶向BCR-ABL1融合的酪氨酸激酶抑制剂(TKI)已被广泛用于治疗慢性粒细胞白血病(CML)。靶向PML-RARA融合的全反式维甲酸(ATRA)和三氧化二砷(ATO)联合用药已被证明对急性早幼粒细胞白血病(APL)有效。此外,高剂量阿糖胞苷(HDAC)治疗显著改善了核心结合因子(CBF)急性髓系白血病(AML)患者的预后。因此,对融合基因的研究可能通过在未来提供更多诊断标志物和治疗方法,使白血病患者受益。
本综述聚焦于融合基因的历史、形成机制以及针对白血病中特定融合基因的治疗方法。