Figure 4.

CARMA/CARD-dependent and-independent MALT1 activation. (A) In the depicted T cell malignancies, gain-of-function mutations in CARMA1 or its upstream regulators or in-frame gene fusions of the T-cell co-receptor CD28 with ICOS or CTLA-4 are thought to promote MALT1 constitutive activation. (B) In the indicated B-cell lymphomas constitutive MALT1 protease activity can be driven by oncogenic mutations in CARMA1, CD79A or CD79B, which may be relevant in combination with self-antigen recognition. A subset of MCL and CLL are also addicted to this pathway by unknown mechanisms. (C) A large proportion of MALT lymphoma harbors a chromosomal translocation leading to formation of an oncogenic MALT1-API2 fusion protein. (D) In primary effusion lymphoma (PEL), NF-κB is activated through viral latency proteins such as K13 and K15, which activate NF-κB directly or via MALT1-BCL10. (A,B), mutations and self-antigen are depicted with a yellow star. (A,D) Open questions are depicted with red question marks. PTCL, peripheral T-cell lymphoma; ATLL adult T-cell leukemia/lymphoma; ABC, activated B-cell subtype; DLBCL, diffuse large B-cell lymphoma; BENTA, B-cell expansion with NF-κB and T-cell anergy; MCL, mantle cell lymphoma; CLL, chronic lymphocytic/leukemia.