The API2/MALT1 fusion product may lead to germinal center B cell lymphomas by suppression of apoptosis.
Low-grade B cell lymphomas of mucosa-associated lymphoid tissue (MALT) represent a distinct clinicopathological entity that arises in a wide variety of extranodal sites. Genetically, MALT lymphomas are characterized by the t(11;18)(q21;q21). The genes involved in this translocation have been identified to be API2 on chromosome 11, which encodes an apoptotic inhibitor, and MALT1, a novel gene on chromosome 18. We identified the t(11;18)(q21;q21) by Southern blot analysis and reverse transcriptase PCR in 42% of a panel of extranodal MALT lymphomas. We also identified the breakpoints within the API2 and MALT1 genes in 7 patients, which revealed a consistent breakpoint after the third baculoviral inhibitor of apoptosis repeat domain within API2, and variable breakpoints in MALT1. We determined the API2/MALT1 fusion transcript in 2 cases by Northern blot analysis and also showed that MALT1 mRNA is constitutively expressed in a variety of human tissues. To understand the functional consequence of the translocation, we determined the pattern of expression of API2 and MALT1 through B lineage differentiation. API2 was expressed only in cell lines which correspond to mature B cells, whereas MALT1 mRNA was detectable in pre-B cells, mature B cells and plasma cells. These results suggest that fusion of MALT1 to API2 mediated by the t(11;18)(q21;q21) may result in an increased inhibition of germinal center B cell apoptosis and subsequent development of MALT lymphomas.
Stoffel
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Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. stoffea@rockvax.rockefeller.edu
Le Beau
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D017209:Apoptosis; D001402:B-Lymphocytes / Q000378:metabolism; D015152:Blotting, Northern; D015139:Blotting, Southern; D020169:Caspases; D002454:Cell Differentiation; D015870:Gene Expression; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics* / Q000473:pathology; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012313:RNA / Q000032:analysis; D017423:Sequence Analysis, RNA; D014178:Translocation, Genetic
D051034:Inhibitor of Apoptosis Proteins; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D011506:Proteins; D012313:RNA; D020169:Caspases; C400109:MALT1 protein, human; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein