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）是一种独特类型的T细胞或空细胞表型非霍奇金淋巴瘤，具有独特的形态学特征和CD 30抗原表达。该实体的特征在于t（2;5）染色体易位，导致称为NPM-ALK的嵌合蛋白的表达。NPM-ALK是一种酪氨酸激酶，可与许多衔接蛋白相互作用，并激活参与细胞增殖、转化和存活的几种关键信号通路。我们最近报道了ALCL中转录因子CEBP β的异常表达，并证明CEBP β的表达依赖于NPM-ALK激酶活性。然而，目前还不清楚这种信号是如何转导的，以及这种转录因子表达在ALCL发病机制中的生物学效应。因此，本研究的目的是：1）分析可能参与CEBP β调控的不同途径，包括与NPM/ALK信号传导有关的STAT 3途径、AKT-mTOR途径和MAPK途径; 2）CEBP β表达对存活和增殖的生物学影响，以及ALCL细胞的表型变化特征。

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.