The regulation and biological function of C/EBPbeta overexpression in ALK+ anaplastic large cell lymphoma

ALK+间变性大细胞淋巴瘤（ALCL）是一种不同类型的T细胞或零细胞表型的非霍奇金淋巴瘤，具有独特的形态学特征和CD30抗原表达。这种实体的特征是t（2;5）染色体易位，导致一种称为NPM-ALK的嵌合蛋白的表达。NPM-ALK是一种酪氨酸激酶，它与许多接头蛋白相互作用，并激活参与细胞增殖、转化和存活的几个关键信号通路。我们最近报道了ALCL中转录因子CEBPß的异常表达，并证明CEBPß的表达依赖于NPM-ALK激酶活性。然而，目前尚不清楚该信号是如何转导的，以及该转录因子表达在ALCL发病机制中的生物学作用。因此，本研究的目的是：1)分析可能参与CEBPß调控的不同途径，包括与NPM/ALK信号传导有关的STAT3途径、AKT-mTOR途径和MAPK途径；2)CEBPß表达在ALCL细胞存活和增殖中的生物学后果以及表型变化特征。

ALK+ Anaplastic Large Cell Lymphoma (ALCL) represents a distinct type of non-Hodgkin lymphoma of T- or null-cell phenotype with unique morphological features and CD30 antigen expression. This entity is characterized by the t(2;5) chromosomal translocation, resulting in the expression of a chimeric protein called NPM-ALK. NPM-ALK is a tyrosine kinase that interacts with many adaptor proteins and activates several key signalling pathways involved in cell proliferation, transformation, and survival. We recently reported the abnormal expression of the transcription factor CEBPß in ALCL, and demonstrated that CEBPß expression is dependent on NPM-ALK kinase activity. However, it is unclear how this signal is transduced and what are the biological effects of the expression of this transcription factor in the pathogenesis of ALCL. Therefore, the aims of this study are 1) to analyze the different pathways that might be involved in the regulation of CEBPß, including the STAT3 pathway, the AKT-mTOR pathway and the MAPK pathway that have been implicated in NPM/ALK signalling, and 2) the biological consequences of CEBPß expression in survival and proliferation, as well as phenotypical changes characteristic of ALCL cells.