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Pathogenesis of MALT lymphoma: Implications for risk stratification and therapy

That cytogenetic and molecular genetic abnormalities have major implications for the therapy of haematological malignancy is now beyond doubt: the prognostic implications of, say, t(15:17) and t(8:21) are now incorporated into therapeutic strategies in AML, as are those of the 17p deletions in designing new therapies in CLL. In multiple myeloma too, the independent prognostic significance of translocations such as t(4:14) is increasingly recognised. Conventional karyotyping has its obvious limitations especially when tissue cannot readily be disaggregated or where the number of cells in cycle is low, but PCRand FISH-based technologies can provide useful diagnostic and prognostic information in the settings of lymphoma and a panel of FISH probes may provide rapidly available information in a broad spectrum of haematological malignancies. In lymphoma and general and low grade lymphoma in particular, such approaches have not generally been incorporated yet into standard diagnostic practice and the paper by Xiaoyan and colleagues provides further confirmation of the value of assessing chromosomal translocations or their molecular counterparts in MALT lymphoma of the stomach. It has been known for some time that t(11;18) is specifically associated with MALT lymphoma [1] and is not detected in other lymphoma subtypes, nor in uncomplicated H. pylori gastritis. Moreover the AP12 – MALT fusion product activates the NF-kB survival pathway in the tumour cells and provides insight into the molecular pathogenesis of the tumour [2]. It has also been known that such tumours respond less well than those without the translocation to H. pylori eradication and perhaps, counter-intuitively have a lower incidence of transformation to higher grades of NHL [3,4]. Using a PCR-based technique, the authors confirm these findings but suggest a different pattern of disease in the Chinese population, perhaps reflecting patterns of exposure to infectious agents that differ from those seen in occidental populations. It will be important to examine both incidence of disease and cytogenetic abnormalities in Chinese populations in the West to establish whether this is a true ethnic variant or relates more to environmental exposure. Furthermore the authors demonstrate a high incidence of BCL-10 expression with bcl-10 protein in both cytoplasm and nucleus [5]. They postulate a role for the interaction of these two abnormalities in pathogenesis and a potential role for BCL-10 in transformation. This suggestion of possible synergy fits well with the observation that BCL-10 links antigen receptor signalling to the NF-kB pathway. This work provides further confirmation of the utility of cytogenetics in MALT lymphoma of the stomach. By utilising FISH technology patients can be readily stratified into t(11:18) 7ve and þve groups. The former can be treated with H. Pylori eradication alone in the confident expectation of a useful and durable response, with the proviso that careful endoscopic follow-up is required to ensure patients do not relapse with transformed disease. A low level of bcl-10 nuclear expression in primary or follow-up samples may provide some additional reassurance. Those patients with t(11;18) are unlikely to respond to H. pylori eradication alone and will require additional therapy; whether anti-CD20 antibodies add substantially to the remission duration achievable with alkylating agents alone remains to be established.