From MALT lymphoma to the CBM signalosome Three decades of discovery

The advent of molecular cytogenetics has led to the elucidation of genetic abnormalities that cause various congenital and oncological disorders. In B-cell lymphoma, for example, a number of chromosomal translocations have been identified in and associated with the etiology of specific subtypes of lymphoma. Several recurrent chromosomal translocations have been identified in extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). Cloning and characterization of the products of three mutually exclusive translocation breakpoints found in MALT lymphoma led to the discovery of a novel NF kappa B-activating complex comprising the CARMA, Bcl10 and MALT1 proteins. This CBM signalosome acts downstream of the antigen receptors in lymphocytes as well as a number of non-lymphoid cell-surface receptors involved in a variety of biological processes. CBM signalosome activity is important for normal cellular functions and is perturbed in neoplastic and inflammatory disorders, making it a viable target for novel therapeutic design.