基于慢性粒细胞白血病（CML）致病驱动分子BCR-ABL融合蛋白的靶向治疗（伊马替尼，IM）使CML的疗效显著改善，但仍存在对IM耐药及复发，除了与ABL基因突变之外，尚有许多未明确分子机制。我们研究发现，亚核体paraspeckles的结构支架长链非编码RNA（lncRNA） NEAT1的表达受到c-Myc调控并与抗IM诱导的细胞凋亡密切相关，提示BCR-ABL可能通过c-Myc调控NEAT1及paraspeckles在细胞凋亡中的作用。本课题拟研究①BCR-ABL对NEAT1表达及paraspeckles的影响；②c-Myc抑制NEAT1表达的机制；③NEAT1调控的paraspeckles在CML细胞凋亡中的功能机制。本研究将进一步明确BCR-ABL的新的分子作用机制；阐明NEAT1的表达调控及作用机制，探讨其在抗IM诱导的细胞凋亡中的作用，为改进CML的治疗提供新的思路和实验线索。

Chronic myeloid leukemia (CML) is a clonal disease characterized by the presence of a constitutively active tyrosine kinase BCR-ABL oncoprotein. Although BCR-ABL is crucially important for pathogenesis and responsiveness to imatinib treatment, it is thought that some additional factors might involve in regulation of this process. We found that nuclear enriched abundant transcript1 (NEAT1), an lncRNA essential for the formation of nuclear body paraspeckles, is significantly repressed in in CML patients samples compared with those of healthy donors. We found that NEAT1 expression was repressed by BCR-ABL, and the expression of NEAT1 could be restored after treatment with imatinib. Importantly, NEAT1 was shown to be regulated by c-Myc in K562 cells, suggesting that NEAT1 and paraspeckles may play an important role in BCR-ABL-mediated CML. Here, we will explore the molecular mechanism of BCR-ABL/c-Myc-mediated regulation of NEAT1. Further,we will investigated the effect of NEAT1 and paraspeckles in imatinib-induced apoptosis of CML cells. Understanding the mechanisms of NEAT1 regulation and its roles in CML cells apoptosis may lead to a fuller understanding of the molecular events leading to CML, and provide novel potential targets for CML diagnosis and therapy.