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)是一种具有独特形态特征和CD30抗原表达的T细胞或空细胞表型的非霍奇金淋巴瘤。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，激活几个关键的信号通路，参与细胞的增殖、转化和生存。我们最近报道了转录因子CEBP？在ALCL中的异常表达，并证明了CEBP？的表达依赖于NPM-ALK的活性。然而，目前还不清楚这一信号是如何传递的，以及该转录因子的表达在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CEBP？调控的不同途径，包括参与NPM/ALK信号转导的STAT3通路、AKT-mTOR通路和MAPK通路；2)CEBP？表达对生存和增殖的生物学影响，以及ALCL细胞的表型变化。

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.