m6A(N6-甲基腺嘌呤)甲基化是一种常见的mRNA修饰方式，由甲基化酶METTL3等调控；可参与mRNA剪切、造血干/祖细胞分化、白血病细胞恶性克隆的形成等。t(8;21)急性髓系白血病（AML）因染色体异位形成的AML1-ETO(AE)融合蛋白是此型白血病发生的始动因素，但需要另一种打击（如c-KIT突变等）才能导致白血病。不同于AE蛋白，选择性剪切体AE9a可直接致小鼠白血病发生，其可能是一种新的 “二次打击”。我们前期研究结果示AE阳性白血病细胞METTL3表达明显高于敲除AE基因的同一细胞系、AE阳性白血病细胞m6A甲基化明显升高。因此，我们假设METTL3受AE调控，经m6A甲基化修饰mRNA,促进剪切体AE9a形成，参与白血病发生。本研究将通过白血病细胞系体外分析、动物体内实验及白血病患者临床标本检测，证明METTL3通过m6A甲基化促进AE9a形成并导致白血病发生发展。

M6A methylation is a common mRNA modification which regulated by methylase METTL3, it participate mRNA splicing, Hematopoietic stem/progenitor cell differentiation and Formation of malignant clones of leukemia cells. AML1-ETO(AE) fusion protein combine with another hit (eg. C-KIT mutation) are the origin of t(8,21) AML. Other than AE protein, selective Spliceosome AE9a can directly lead to leukemia in mice, so we guess it may serve as a novel “second hit”. Our previous research indicated that the AE-positive leukemia cell expressed more METTL3 than AE-negative cell line, and the m6A methylation is higher in AE-positive cell line. Given all the above, we assumed that METTL3 is regulated by AE，and methylated by m6A which give rise to the formation of spliceosome AE9a and finally result in leukemia. Our research try to prove this process through the analysis of in vitro study of leukemia cell line, experiment in animal as well as sample of patients.