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

• Applicant: Professor Dr. Falko Fend
• Subject Area: Pathology
• Term: from 2007 to 2009
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 52958125

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.

• DFG Programme: Research Grants
• Participating Person: Professorin Dr. Leticia Quintanilla-Martinez de Fend