急性粒细胞性白血病（AML）是一类髓系造血细胞常见的恶性肿瘤，AML特异性T（15，17）染色体发生易位产生的融合蛋白PML-RARα是AML-M3发病的罪魁祸首。研究表明TRB3在正常组织中局限表达于肝脏，我们发现TRB3高表达于AML细胞，干扰TRB3表达增加AML的细胞分化和凋亡能力。自噬活性变化参与AML发生、发展过程，PML-RARα通过自噬途径进行降解。我们发现TRB3在肿瘤细胞内发挥抑制自噬的功能，并且与PML-RARα存在相互作用。本项目拟进一步确认TRB3在AML疾病进展中的作用，明确TRB3/PML-RARα相互作用是否稳定PML-RARα。我们还将根据TRB3/PML-RARα相互作用结构域筛选抑制其相互作用的α螺旋肽，观察该α螺旋肽是否具有抑制AML的作用。本研究将有助于我们深入理解TRB3参与AML发展的分子机制，为开发新的治疗AML的辅助药物提供理论和实验依据。

Acute myelogenous leukemia (AML) is a common type of myeloid hematopoietic malignancies, and most AML-M3 cases are characterized by the formation of the PML-RARα fusion protein which is resulted with t(15;17) translocation. Previous studies indicated that TRB3 expression was limited to liver tissue. We found that TRB3 expression was enhanced in AML cells and silencing of TRB3 induced differentiation and apoptosis of AML cells. Leukemia initiation and progression are associated with autophogy with unclear mechanism. The previous studies have implicated the autophagy-lysosome pathway as the main mechanism involved in therapy-induced PML-RARα degradation. Here we report that isotopic expression of TRB3 inhibited autophagy and TRB3 physically interacted with PML-RARα in AML cells. Hence, we intend to confirm the role of TRB3 in AML progression and whether the TRB3/PML-RARα interaction inhibit autophagy-dependent PML-RARα degradation. We next investigate the interacting domain of TRB3/PML-RARα and screen short α-helical segments to interrupt TRB3/PML-RARα interaction. We will evaluate whether treatment of α-helical peptides inhibit AML cell progression in vitro and in vivo. Our study will provide novel insights into understanding of TRB3 in the regulation of leukemia progression, and will provide theoretical and experimental data for the new anti-AML drugs discovery.