Molecular analysis of malignant lymphoma-related oncogenes and its clinical application for diagnosis and treatment.

1）API2-MALT 1。t（11; 18）（q21; q21）是粘膜相关淋巴组织（MALT）型淋巴瘤中的特征性染色体易位，并且该易位导致API 2（凋亡抑制剂2，也称为c-IAP 2）-MALT 1（粘膜相关淋巴瘤易位基因1）的嵌合转录物。为了鉴定结合API 2-MALT 1嵌合蛋白的蛋白，我们采用免疫共沉淀和SDS PAGE分析，然后通过液相色谱-电喷雾串联质谱。结果，Smac、Htra 2和TRAF 2被鉴定为API 2-MALT 1结合蛋白。免疫沉淀分析表明，异位表达的API 2-MALT 1蛋白确实结合这些内源性蛋白。此外，API 2-MALT 1蛋白显着抑制Smac促进的细胞凋亡在紫外线照射的HeLa细胞。这些数据有力地表明，API 2-MALT 1可以通过抑制Smac介导的凋亡途径来至少部分地阻断凋亡。BCL-6/LAZ 3基因编码一个锌指， ...更多信息 r转录抑制因子，位于非霍奇金淋巴瘤（NHL）中最常发生的3q 27相关翻译的断点。为了检测与BCL-6信号传导途径相关的细胞应答和靶基因，我们建立了携带人BCL-6转基因的Ba/F3 pro-B细胞，该转基因在乳糖操纵子的控制下是可诱导的。利用cDNA阵列杂交技术，我们发现诱导的BCL-6蛋白可以下调基因cyclin A2的表达。Ba/F3细胞中的趋化因子受体CXCR 4和胰岛素样生长因子结合蛋白-4（IGFBP-4）。北方印迹分析证实，这些基因的表达确实被诱导的BCL-6蛋白下调，但方式略有不同。诱导表达的BCL-6蛋白对Ba/F3细胞的增殖也有抑制作用。这些发现有力地表明，三个关键基因，即细胞周期蛋白A2，CXCR 4和IGFBP-4可能在B淋巴细胞分化过程中的BCL-6信号通路的下游发挥作用。少

1)API2-MALT1. t(11;18)(q21;q21) is a characteristic chromosomal translocation in mucosa-associated lymphoid tissue(MALT) type lymphoma, and this translocation results in chimeric transcript of API2(APoptosis Inhibitor 2,also known as c-IAP2)-MALT1(Mucosa-Associated Lymphoma Translocation gene 1). To identify proteins that bind API2-MALT1 chimeric protein, we employed coimmunoprecipitation and SDS PAGE analysis, followed by liquid chromatography-electrospray ionization tandem mass spectrometry. As a result, Smac, Htra2,and TRAF2 were identified as API2-MALT1-binding proteins. Immunoprecipitation analysis demonstrated that ectopically expressed API2-MALT1 protein indeed binds to these endogeneous proteins. Furthermore, API2-MALT1 protein significantly inhibited Smac-promoted apoptosis in UV irradiated HeLa cells. These data strongly suggest that API2-MALT1 can block apoptosis, at least in part, by inhibiting Smac-mediated apoptotic pathway.2)BCL6. The BCL-6/LAZ3 gene encodes a zinc-finge … More r transcriptional represser and is located at the breakpoint of the 3q27-associated translations that occur most frequently in non-Hodgkin's lymphomas (NHLs To examine cell responses and target genes related to the BCL-6 signaling pathway, we established Ba/F3 pro-B cells carrrying a human BCL-6 transgene that is inducible under control of the lactose operon. Using a cDNAarray hybridization technique, we found that the induced BCL-6 protein can downregulate the expressions of the genes, cyclin A2. chemokine receptor CXCR4,and insulin-like growth factor binding protein-4(IGFBP-4) in the Ba/F3 cells. Northern blot analysis established that the expressions of these genes were indeed downregulated by the induced BCL-6 protein but in a somewhat different manner. The induced BCL-6 protein also inhibited cell proliferation of Ba/F3 cells. These findings strongly suggest that three key genes, namely cyclin A2,CXCR4 and IGFBP-4 may play a role in the downstream of the BCL-6 signaling pathway during B-lymphoid differentiation. Less