急性淋巴细胞白血病（ALL）是常见的成人急性白血病。中枢神经系统白血病（CNSL）是ALL常见并发症，是缓解期ALL复发和死亡重要因素之一。目前观点认为白血病细胞浸润中枢神经系统的主要机制是通过血脑屏障，但是其分子水平调控机制尚不清楚。本课题组前期数据表明CD56表达是ALL发生CNSL的独立风险因子，在培养的CD56-和CD56+的ALL细胞株中NF-κB存在差异表达。通过String蛋白网络分析数据库分析出CD56的调控蛋白：Snail1。我们采用体外共培养CD56-或CD56+的ALL细胞株和脑微血管内皮细胞（BMECs）、基因敲除和基因干扰技术以及裸鼠ALL模型构建等方法证实抗原分子CD56接触BMECs并通过NF-κB通路调控Snail1蛋白表达，证实Snail1能降解血脑屏障内皮细胞紧密连接相关蛋白。CD56分子通过NF-κB通路破坏血脑屏障机制为临床的预防和治疗奠定基础。

Acute lymphoblastic leukemia (ALL) is a common type of acute leukemia in adult, with a propensity for post-therapeutic recurrence in the central nervous system (CNS). Central nervous system leukemia (CNSL) is an important factor associate with recurrence and death of ALL in complete remission. To cause CNSL, leukemia cell must penetrate the blood-brain barrier (BBB), which consists of an extremely specialized layer of brain microvascular endothelial cells (BMECs). However, the direct molecular mechanisms that regulate cellular BBB disruption and penetration are still remains unclear. In our previous work, multivariate analysis revealed CD56 expression to be statistically significant risk factors for CNS involvement, we had isolated CD56- and CD56+ ALL cell lines from the leukemia cell of human bone marrow and cerebrospinal fluid (CSF), respectively, NF-κB was found to be differentially expressed in CD56- ALL cell line versus CD56+ ALL cell line. There are many transcription factor that may interact with the CD56, such as Snail1. During the development of the CNSL, damage is a common event, and it is primarily mediated by the activation of Snail1. We propose a new idea to our study: Snail1 production starts in the BMECs following NF-κB activation caused by direct contact of the CD56 cell surface antigen. Further studies could be carried out to confirm the findings of our study, such as co-culture of healthy human BMECs and CD56- or CD56+ ALL cell lines, gene knockout and RNA interference technology, building of ALL model in nude mice. NF-κB mediates transcriptional activation of snail through interactions with CD56, snail1 increased the permeability of CD56+ cell via NF-κB mediated degradation of JAM-1、ZO-1、claudin-5 and occludin. The molecular mechanisms that that there is a NF-κB signaling pathways activation for leukemia cell across the BBB, which could be regulated by CD56. The findings are beneficial for researchers to understand the etiology of CNSL and to lay a solid foundation for the prevention of CNSL.