ORGANIZATION AND CONTROL OF GENETIC MATERIAL IN PLASMACYTOMAS

我们的研究目标是识别和理解哪些基因改变了 结构或表达在恶性肿瘤、免疫反应中起关键作用 疾病与正常分化。我们现在关注的是 一组癌基因的表达：abl、bcl2、myb和myc，AS 以及潜在的癌基因Pvt-1和蛋白激酶C(PKC)，在 小鼠造血肿瘤。解除对myc表达的调控继发于 染色体易位已被证明是 石油诱导的I.P.的基因改变。中国的浆细胞瘤 Balb/c小鼠。其中一些激活myc的易位发生在200-300之间 在一个叫做Pvt-1的区域，c-myc的Kb 3‘，我们已经证明了这一点 基因座在正常细胞中转录水平很低，但在许多细胞中 在某些浆细胞瘤中含量较高。正常情况下，PVT-1的转录本是CA。 14kb，表明pvt-1基因座很大。在一些 Pvt-1基因座有染色体易位的浆细胞瘤。这个 PVT-1转录本被截短并与Ig kappa链形成嵌合体 成绩单。 我们已经分离了小鼠bcl-3(位于人类19号染色体上)的cdna，并获得了 将其映射到小鼠的7号染色体上。在B细胞分化过程中 在没有经历过Ig同型转换的细胞中表达最多。 这表明涉及该基因的染色体易位 这是发生在这个阶段的一些CLL的特征。 表达v-abl和c-myc的ABL-myc逆转录病毒可迅速诱导 BALB/c等品系小鼠的腹膜内浆细胞瘤，甚至 在没有IP的情况下。并且在没有辅助病毒的情况下。如果 小鼠用溶菌酶或绵羊红细胞预免疫，约60% 发展产生针对该基因的抗体的肿瘤 免疫基因。这可能被证明是杂交瘤的一个有用的替代品。 产生单抗的技术。

Our research goal is to identify and understand the genes whose altered structure or expression play critical roles in malignancy, immune diseases and normal differentiation. We are concentrating on the expression of a group of these "oncogenes": abl, bcl-2, myb, and myc, as well as the potential oncogenes, Pvt-1 and Protein Kinase C (PKC), in mouse hemopoietic tumors. Deregulated expression of myc secondary to chromosome translocation has been shown to be one essential component of the genetic alterations involved in oil-induced i.p. plasmacytomas in BALB/c mice. Some of these myc-activating translocations occur 200-300 kb 3' of c-myc in a region called Pvt-1, and we have shown that this locus is transcribed at very low levels in normal cells but in much higher amounts in some plasmacytomas. Normally Pvt-1 transcripts are ca. 14 kb in length, suggesting that the Pvt-1 locus is very large. In some plasmacytomas with chromosomal translocations in the Pvt-1 locus. the Pvt-1 transcripts are truncated and form chimeras with Ig kappa chain transcripts. We have isolated a cDNA for mouse bcl-3 (on human chromosome 19) and have mapped it to mouse chromosome 7. During B-cell differentiation its expression is maximal in cells that have not undergone Ig isotype switch. This suggests that the chromosome translocations involving this locus that characterize some CLL's occur in this stage. The ABL-MYC retrovirus, expressing v-abl and c-myc, rapidly induces intra-peritoneal plasmacytomas in BALB/c and other strains of mice, even in the absence of i.p. oil and in the absence of helper virus. If the mice are preimmunized with lysozyme or sheep red blood cells, about 60% develop tumors producing antibody specifically directed against the immunogen. This may prove to be a useful alternative to hybridoma technology for generating monoclonal antibodies.