BCR-ABL酪氨酸激酶抑制剂是治疗慢性粒细胞白血病（CML）的主要药物，但部分患者会产生抗药性，制约着其疗效，其耐药机制仍未阐明。我们前期研究发现MLKL高表达与CML耐药相关。本研究拟以流式细胞术及非还原性凝胶电泳等技术，对CML中MLKL表达水平及存在状态进行检测，分析MLKL高表达与CML靶向治疗疗效的关系及其临床意义；同时，以分子生物学方法验证HSP90调控MLKL以激活NLRP3炎性因子并释放IL-1β进而导致CML耐药的分子调控机制；以酵母文库筛选调控MLKL高表达的新信号分子，研究其在激活HSP90/MLKL/NLRP3、介导CML耐药中的作用及其信号通路。本研究将揭示MLKL在CML中的表达水平、存在状态及调控规律，阐明MLKL功能状态与CML耐药的关系及其机理，为克服BCR-ABL酪氨酸激酶抑制剂的耐药提供新策略，为慢性粒细胞白血病的治疗提供新的靶点。

BCR-ABL tyrosine-kinase inhibitors are the main drugs used to treat chronic myelogenous leukemia (CML). However, CML in some patients have developed resistance. This results in unfavorable curative effect and the detailed mechanism is still to be clarified. Our previous work found that the high level of MLKL does relate to resistance of CML. In this study, we will detect the expression level and existential state of MLKL in CML by using flow cytometry and non-reducing polyacrylamide gel electrophoresis methods, then analyze the relationship between the high expression level of MLKL and the curative effect of targeted therapy to CML and its clinical significance. Meanwhile, we will attend to validate the molecular mechanism by which HSP90 modulates MLKL in activating inflammatory factor NLRP3. NLRP3,once been activated,can initiate the release of IL-1β which then results in resistance of CML. We will also screen yeast library to find new proteins which can regulate the high expression level of MLKL, and then study their functions in activating HSP90/MLKL/NLRP3 pathway and resistance of CML. In brief, this study is devoted to reveal the expression level, existential state and regulation rules of MLKL in CML, to illustrate the relationship between the functional status of MLKL and resistance of CML and its mechanism. The ultimate goal of research is to provide new insights into the drug resistance problem that BCR-ABL tyrosine-kinase inhibitors facing and to seek for new targets of CML treatment.