Die molekulare Pathogenese des klassischen Hodgkin-Lymphoms [The molecular pathogenesis of classical Hodgkin lymphoma]

Despite the fact that classical Hodgkin lymphoma (HL) has been described more than 170 years ago, only over the last 15 years significant advances regarding its molecular pathogenesis have been achieved. The lack of a specific lineage profile in combination with the low number of the malignant mononuclear Hodgkin- and multinucleated Reed-Sternberg- (HRS-) cells in the affected lymph nodes prevented for a long time both the identification of its cell of origin and of genomic and molecular defects. The development of methods for the analysis of micromanipulated single cells made it possible to demonstrate a B cell origin of HRS cells. However, it has become clear that the normal B cell-specific gene expression program in HRS cells is disrupted by various molecular lesions. Furthermore, molecular and genomic defects of various signaling pathways could be identified in HRS cells, including the NF-kappaB, JAK/STAT and MAPK-AP-1 signaling pathways, which protect HRS cells from apoptotic cell death. Despite significant advances in the treatment of HL, the considerable long term toxicity of conventional therapies requires the development of new non-genotoxic therapeutic strategies. Therefore, it will be a central aim to develop new treatment strategies based on these insights into HL pathogenesis.