基于ID1竞争性靶向重构AETFC抑制t（8；21）急性髓系白血病的研究

AETFC是在AML细胞中发现的多蛋白复合物，它除了包含致病融合蛋白AML1-ETO，还包含E-box结合蛋白（E蛋白）以及与E蛋白结合的LYL1，因此AETFC可以结合到E-box位点上。ID蛋白通过与E蛋白形成异源二聚体，行使负调控功能。有趣的是，ID1虽然在造血干细胞和AML干细胞中均有表达，但并不参与AETFC组成，这提示ID1对于AETFC介导的白血病发生可能具有重要作用。我们前期研究发现，ID1可以通过与LYL1的竞争作用改变AETFC的稳定性，从而使AETFC在基因组上的结合模式发生改变，并且具有抑制细胞增殖的功能。本项目旨在利用ID1与LYL1竞争结合E蛋白从而破坏AETFC复合物稳定性的特点，设计和开发与E蛋白亲和力更强的ID1短肽作为更好治疗AML1-ETO白血病的靶向药物。这将有助于我们加深理解t（8；21）白血病的发病机制，并为该型白血病的治疗提供新的策略。

The AML1-ETO-containing transcription factor complex (AETFC) is a multiprotein complex that was identified from acute myeloid leukemia (AML) cells. Except for the leukemogenic fusion protein AML1-ETO, this complex also contains E-box binding proteins (E proteins) and LYL1 which binds to E proteins, thus AETFC can bind to E-box. ID proteins perform a negative regulatory function by forming heterodimers with E proteins. Interestingly, although ID1 is expressed in both hematopoietic and AML stem cells, it is not involved in AETFC composition, which suggests that ID1 may play an important role in the occurrence of AETFC-mediated leukemia. Our previous study found that ID1 can change the stability of AETFC by competing with LYL1, changing the binding mode of AETFC on the genome and inhibiting cell proliferation. Based on the characteristics of ID1 and LYL1 that competitively bind E protein to destroy the stability of the AETFC complex, this project plans to design ID1 peptides with stronger affinity for E protein as a targeted drug for better treatment of AML1-ETO leukemia. This project should not only contribute to a better understanding of the mechanisms of leukemogenesis, but also provide new therapeutic strategies for t(8;21) leukemia treatment.