Stoffel A, Le Beau M M
Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Hum Hered. 2001;51(1-2):1-7. doi: 10.1159/000022952.
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.
黏膜相关淋巴组织（MALT）低度B细胞淋巴瘤是一种独特的临床病理实体，可发生于多种结外部位。在基因方面，MALT淋巴瘤的特征是t(11;18)(q21;q21)。已确定参与此易位的基因在11号染色体上为API2，其编码一种凋亡抑制剂，在18号染色体上为MALT1，这是一个新基因。我们通过Southern印迹分析和逆转录酶PCR在一组结外MALT淋巴瘤中42%的病例中鉴定出了t(11;18)(q21;q21)。我们还在7例患者中鉴定了API2和MALT1基因内的断点，结果显示API2内第三个杆状病毒凋亡抑制重复结构域之后有一个一致的断点，而MALT1中的断点则各不相同。我们通过Northern印迹分析在2例病例中确定了API2/MALT1融合转录本，还表明MALT1 mRNA在多种人体组织中持续表达。为了解该易位的功能后果，我们通过B淋巴细胞分化确定了API2和MALT1的表达模式。API2仅在对应于成熟B细胞的细胞系中表达，而MALT1 mRNA在前B细胞、成熟B细胞和浆细胞中均可检测到。这些结果表明，由t(11;18)(q21;q21)介导的MALT1与API2融合可能导致生发中心B细胞凋亡抑制增加，进而引发MALT淋巴瘤。
