化疗耐药是慢性粒细胞白血病（CML）临床治疗中亟待解决的问题，探索新的治疗靶点或化疗增敏靶点有重要意义。现有研究及我们的前期结果提示，Bcl-x基因在CML中发生异常选择性剪接，该异常剪接是CML进展和化疗耐受的关键分子基础。基于此我们提出假说：以特殊技术直接调控Bcl-x异常剪接有助于CML的治疗和化疗增敏。本项目中我们将应用具有明显优越性的Vivo-Morpholinos技术调控Bcl-x剪接，通过CML细胞株、CML患者骨髓原始细胞、裸鼠移植瘤模型及血液肿瘤模型，采用real time PCR、western blot、流式细胞术、药物敏感性实验等手段，从分子、细胞、组织及动物整体水平等多方面探讨Bcl-x剪接调控在CML治疗及化疗增敏中的作用及机制。并进一步探索Bcl-x剪接调控策略与常规化疗药物的有效组合，为临床耐药CML的治疗和化疗增敏提供理论和实验依据。

Chemotherapy-resistance is a pressing issue in chronic myeloid leukemia (CML) treatment. Exploring new therapeutic targets or chemotherapy sensitization targets is important. Previous studies and our results revealed that aberrant Bcl-x alternative splicing occours in CML and is related to chemotherapy-resistance and development of CML. Based on these, we propose a hypothesis: the targeted rectification of Bcl-x aberrant splicing will be conducive to CML treatment and chemotherapy sensitization. In order to prove this hypothesis, the Vivo-Morpholinos technology will be used to regulate Bcl-x splicing; the CML cell line, primitive bone marrow cells of CML patients, nude mouse transplantation tumor model and blood tumor model will be studied by real time PCR, western blot, flow cytometry, and drug sensitivity test. Additionally, we will make a further exploration on the effective combinations of Bcl-x splicing regulation and chemotherapy drugs in CML treatment. In short, the main objective of this project is to carry out an exceptionally useful exploration work for discovering new therapy target and chemotherapy sensitization target of CML.