The NF-kappaB signalling pathway: a therapeutic target in lymphoid malignancies?

Nuclear factor-kappaB/reticuloendotheliosis (NF-kappaB/Rel) designates a family of transcription factors that influence the activation of a multitude of genes critically involved in immune and inflammatory responses. Recently, genetic and biochemical evidence has accumulated, suggesting that constitutive activation of NF-kappaB/Rel proteins plays an important role in the development/progression of B and T cell lymphoid malignancies. In particular, genetic and molecular alterations of NF-kappaB family members and their transcriptional target genes have been implicated in the development of diffuse large B cell lymphoma and mucosa-associated lymphoid tissue lymphoma. Although NF-kappaB/Rel proteins represent an integrating point of several pathways, potentially contributing to several diseases, their unique activation depends on cell type and stimulus. Considering the NF-kappaB specificity in lymphoid cells, molecules that finely modulate the activity of these NF-kappaB components and dampen the inappropriate proliferation of lymphocytes may represent a novel pharmacological intervention to several lymphoid malignancies.