Marginal-zone B-cell lymphoma of extranodal mucosa-associated lymphoid tissue type: Molecular genetics provides new insights into pathogenesis

Marginal zone B-cell lymphoma of extranodal mucosa-associated lymphoid tiss ue (MALT) type is recognized as a distinct clinicopathologic entity in the revised European-American lymphoma (REAL) and recently published World Heal th Organization (WHO) classifications. These neoplasms are thought to arise from the extranodal equivalent of the lymph node marginal zone. Two recurr ent chromosomal translocations, to date, have been implicated in the pathog enesis of these neoplasms. The t(11;18)(q21;q21), which is far more common, disrupts the api2 gene on chromosome 11q21 and the malt1 (mlt) gene on chr omosome 18q21, resulting in the synthesis of a novel fusion gene and protei n, AP12-MALT1. The t(1;14)(p22:q32), which is uncommon, juxtaposes the bcl- 10 gene on chromosome 1p22 adjacent to the immunoglobulin heavy chain (IgH) gene on chromosome 14, wherein BCL10 is overexpressed via the influence of the IgH enhancer. BCL-10 may then form a complex with MALT I in the cell. Both translocations result in increased inhibition of apoptosis, conferring a survival advantage. Recent work suggests that AP12-MALT1 and BCL10-MALT1 may activate NF-kB and a common downstream signaling pathway.