Signaling Pathways in Rare Lymphomas

Here we give an overview of select signaling pathways understood or thought to play a key role in the pathogenesis of lymphomas, covering examples of both B-cell and T-cell lymphomas. The selection focuses on providing well-understood examples and may serve as a guideline also for entities not covered in these sections. Remarkably many of these cancers are characterized by genetic alterations that lead to activation of the NF-κB and JAK/STAT pathways. A striking example is seen in MALT lymphoma where recurrent chromosomal translocations targeting different regulatory nodes lead to NF-κB activation. We discuss these mechanisms as well as more disease-specific alterations such as oncogenic activation of MYC in Burkitt’s lymphoma, of TAX in adult T-cell leukemia/lymphoma, of ALK in peripheral T-cell lymphoma, and the MyD88 L265P mutation in Waldenström’s macroglobulinemia. DNA damage pathways are equally of importance and discussed in the context of with mantle cell lymphoma and Burkitt’s lymphoma. A striking example of how dysregulation of immune surveillance pathways interfaces with activation of oncogenic pathways is seen in the case of primary mediastinal B-cell lymphoma