染色体t(8;21)(q22;q22)易位形成AML1-ETO融合基因是白血病中常见的遗传学异常之一，并且在此类白血病的发生发展中起到重要作用。肿瘤相关的染色体易位可以形成融合基因相关的环状RNA(F-circRNA)，F-circRNA由融合基因的线性转录本背部剪接而成，可以促使正常细胞的恶性转化，促进肿瘤细胞的生长并且诱导耐药，在体内亦可促进白血病进程。.本项目拟研究证实AML1-ETO细胞系及病人的白血病细胞中是否存在AML1-ETO相关的融合环状RNA (F-circAE)，进一步通过在MEF细胞中过表达F-circAE，以及在Kasumi-1细胞中干扰F-circAE，探索细胞生物学功能的改变及具体机制，同时建立AML1-ETO&F-circAE白血病小鼠模型，研究F-circAE在体内的作用。该项研究可有助于对t(8;21)白血病发病机理的认知，并为该病提供新的治疗、监测靶点

Chromosome translocation of t(8;21)(q22;q22) is one of the most common genetic alterations in leukemia, generating the fusion gene AML1-ETO, which has been proved to be involved in leukemogenesis. Tumor-associated chromosomal translocations give rise to fusion circRNAs (F-circRNAs) that are back-spliced from transcribed exons of fusion gene. F-circRNAs contribute to the cellular transformation, promote cell viability and resistance to therapy, they can also promote tumor progression in vivo..In this project, we will investigate whether aberrant chromosomal translocation of t(8:21) could produce AML1-ETO associated fusion circRNAs (F-circAE) in AML1-ETO cell lines and patients carrying AML1-ETO fusion genes. In vitro, to express F-circAE in MEF and knock down F-circAE in Kasumi-1 cells, and to investigate whether F-circAE could affect the biological functions. To establish AML1-ETO & F-circAE leukemic murine model, and the functions of F-circAE in vivo will be further investigated and verified. Through this study, it will contribute to better understanding of the molecular mechanisms involved in t(8;21) leukemia onset and progression, and to provide novel monitoring marker and potential therapeutic implication.