TEL/AML1融合基因阳性儿童急性淋巴细胞白血病在白血病中预后较好，但临床发现至少有近20%患者复发。在基因表达层面，调控mRNA选择性剪接的功能基因突变（包括最近发现的mRNA 6-甲基腺嘌呤(m6A)的甲基化修饰蛋白WTAP和YTHDF2），导致造血相关因子选择性剪接形式变化，与血液疾病紧密相关，提示mRNA m6A甲基化修饰可能作为一种新的白血病发生及复发机制。在前期研究中，我们初步对四类临床样本包括正常个体、TEL/AML1阳性治疗效果好未复发患者、难治型患者、复发患者进行转录组测序，发现其它三组疾病个体与正常个体在mRNA中m6A水平和造血相关因子表达和选择性剪接形式存在显著差异，提示TEL/AML1融合基因阳性患者中mRNA的m6A甲基化调控网络参与了白血病相关重要因子的调节。本项目拟重点阐明mRNA甲基化调控TEL/AML1融合基因阳性儿童急性淋巴细胞白血病发生发展机制。

TEL/AML1 fusion gene is the most common mutation in childhood acute lymphoblastic leukemia, which has been considered as a good prognosis molecular marker, but there are 20% patients were relapsed. It has been observed that both the function mutations of mRNA splicing factors including mRNA methylation N6-methyl-adenisine (m6A) modification proteins WTAP protein and YTHDF2, and the alternative splicing variations of hematopoietic factors may attribute to acute lymphoblastic at gene expression level, suggesting that mRNA m6A methylation may present as a novel mechanism of leukemia relapse. In our pioneering study, we initially sequenced transcriptomic profiles of four types of clinical samples including normal individuals (category A) and three type of patients with TEL/AML1 fusion gene mutation-category B: patients who have good response of treatment without relapse; -category C: refractory patients; -category D: relapse patients. We found the three patient groups display significant differences at both the mRNA levels and alternative splicing isoforms of hematopoietic factors and have dramatically increased m6A in mRNA, indicating that the mRNA m6A methylation regulatory networks involve in the regulation of childhood acute lymphoblastic leukemia having TEL/AML1 fusion mutations. The project aims to unveil how the mRNA methylation regulates the development of childhood acute lymphoblastic leukemia carrying TEL/AML1 gene fusion mutations.