PML/RARα是急性早幼粒细胞白血病（APL）的致癌融合蛋白。虽然靶向降解PML/RARα蛋白的药物全反式维甲酸（ATRA）和三氧化二砷（ATO）的成功应用使APL的治愈率得到了较大的提高，但是耐药复发、高危APL以及早期死亡等问题仍然严重威胁部分患者的生命。因此，APL的临床治疗中亟需新的药物或方法来解决这些难题。本项目研究立足于热激诱导PML/RARα蛋白降解的前期发现，以APL细胞株NB4、APL病人原代细胞、外源性表达PML/RARα蛋白的HeLa细胞以及斑马鱼APL模型为研究对象，通过分子细胞生物学、生物化学和药理学等多学科交叉手段，旨在揭示核受体辅阻遏物（NCoRs）在热激诱导PML/RARα融合蛋白降解过程中的作用，深入探究其分子机制，明确热激与ATO可协同诱导PML/RARα蛋白及其耐药突变体降解，为临床治疗APL提供新策略和理论依据。

PML/RARα is the oncogenic fusion protein of acute promyelocytic leukemia (APL). Although the successful application of PML/RARα protein targeted drugs all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has largely improved the cure rate of APL, the problems of drug resistance and relapse, high-risk APL, and early death still pose serious threat to the lives of some patients. Therefore, novel drugs or approaches are urgently needed to solve these problems in the clinical treatment of APL. This project is based on the previous finding of PML/RARα fusion protein degradation by hyperthermia, applying APL cell line NB4, APL patient primary cells, HeLa cells exogenously expressing PML/RARα protein and the zebrafish APL model as research objects, through multidisciplinary means such as molecular cell biology, biochemistry as well as pharmacology, aiming to reveal the involvement of nuclear receptor corepressors (NCoRs) in hyperthermia mediated PML/RARα fusion protein degradation, to explore its molecular mechanism, and to clarify the synergistic effects of hyperthermia with ATO on induction of PML/RARα protein as well as its drug resistant mutants’ degradation, so as to provide a novel strategy and theoratical basis for addressing the remaining problems in the field of APL clinical treatment.