Molecular Events

The molecular events fundamental for MALT lymphoma pathogenesis have been partially dissected. One of the first steps along this pathway is the acquisition of organized lymphoid tissue after a chronic antigenic stimulation by H. pylori. During the prolonged period of lymphoid tissue reactive proliferation, an abnormal B-cell clone arises and replaces the normal population. MALT lymphoma then develops through a series of genetic lesions underlying the progression from a H. pylori-dependent lymphoma—with the presence of H. pylori strain specific T cells necessary for the growth of lymphoma cells—to a H. pylori-independent lesion (Cavalli et al, 2001; Bertoni et al, 2002).

Thirty to 50% of low grade MALT lymphomas carry the t(11;18)(q21;q21) translocation, which is not detected in any other lymphomas, even in MALT lymphomas with large cell components and primary gastric diffuse large B-cell lymphomas. The translocation results in the expression of a chimeric transcript that fuses the apoptosis inhibitor-2 (API2) gene on chromosome 11 to a gene on chromosome 18 called MALT lymphoma translocation (MLT). The normal function of the protein encoded by API2 is to arrest apoptosis. The three domains necessary to suppress apoptosis are always conserved in the chimeric transcript, while its zinc finger domain, which may act as a negative regulator of the apoptosis inhibition, is consistently absent. The function of MLT is still unknown, but it appears to play a role in sub-cellular localization of the chimeric product, which in turn is likely to increase the antiapoptotic effect of API2. The encoded protein contains two immunoglobulin-like C2-type domains, a region homologous with laminin 5a3p, and a domain similar to the mouse immunoglobulin chain VDJ4 sequence. The proportion of MLT that is fused in the expressed transcript is highly variable, due to the varied breakpoints on chromosome 18q.

The t(11;18) appears to be associated with more aggressive clinical behavior. The translocation was present in only 3 of 29 gastric MALT lymphomas confined to the gastric wall but in most of those that disseminated beyond the stomach. Moreover, there is some evidence that it might predict the therapeutic response of gastric MALT lymphoma to H. pylori eradication. In one study, this translocation was absent in all gastric MALT lymphomas that showed complete regression, but it was detected in most of nonre-sponsive tumors, including cases with the disease confined to the gastric wall.

The other recurring chromosomal translocation is t(1;14)(p22;q32) with involvement of BCL-10 on chromosome 1 and the immunoglobulin heavy chain gene on chromosome 14. Wild type BCL-10 is an apoptotic regulatory molecule and acts as a tumor suppressor gene. Aberrant BCL-10 expression occurs frequently without the t(1;14). The combination of t(11;18) and nuclear BCL-10 expression has been reported in advanced gastric MALT lymphomas.

Constipation Prescription

Constipation Prescription

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