Reactive Oxygen Species (ROS) Metabolism –Turning the Sword Against Lymphoma

Chronic inflammatory responses have been shown to promote cancer development at multiple stages[8].90% ofperipheral T cell lymphoma (PTCL)show overexpression of the membrane proximal kinase SYK[9]andin 17% of human PTCL, the recurrent translocation t(5;9)(q33;q22) generates a fusion protein containing the ITK and SYK kinases[10]. This ITK-SYK fusion protein induces antigen-independent TCR signalling that is directly associated with lymphoma formation[11, 12]. In metabolic active malignant cells tight regulation of ROS-detoxifying pathways is required[13]. The PhD candidate will investigatethe function of the antioxidant GSH-GCL complex in a clinical relevant model of PTCL in vivo.In a transgenic mouse model we will express the only known recurrent translocation found inPTCL patients (ITK-SYK). Thus, we are in the position to model the molecular events of human PTCL in a genetic mouse model. Elucidation of signaling and metabolic changes (caused by GCL-deficiency) in the context of PTCL might revealspecific targets for a therapeutic intervention, since currently, treatment options for PTCL are very limited