MECHANISMS UNDERLYING TUMOR DORMANCY

BCL 1白血病是第一个描述的小鼠中的B细胞白血病， 在老年BALB/c小鼠中自发出现。 一个细胞转移到一个 同基因接受者导致进行性白血病， 12周后，肿瘤逐渐生长并死亡。 小鼠 通过致死X射线照射使H-2基因座嵌合， 注射T细胞耗尽同种异体骨髓允许进行性 随后注射的BCL 1细胞的生长。 然而，6周后， 通过独特型分析判断，肿瘤消退，小鼠似乎无肿瘤 血细胞数量、白色血细胞计数和脾脏大小。 疾病不会发生 只要对小鼠进行随访（8个月）。 然而，Cell 转移研究表明脾脏中相对较大的肿瘤负荷（10-6 - 10-7细胞）。 我们将研究肿瘤休眠的生物学， 回答以下问题：1）细胞周期状态是什么？ 休眠细胞 2)他们是否与初始人群不同， 根据免疫表型、对淋巴因子的反应和核型来判断？ 3)什么 是诱导休眠所需的宿主防御机制吗 四、 休眠的自然历史是什么，例如休眠的BCL 1细胞 最终死亡还是当免疫反应增强时它们开始生长 随着年龄的增长而减少？ 5)什么样的干扰可以引发肿瘤生长？ 六、 BCL 1特异性免疫毒素能在体内消除这种休眠细胞群吗？ 关于肿瘤休眠的同源模型，对BCL 1的免疫 肿瘤已经在先前用免疫的BALB/c小鼠中产生 纯化的BCL 1-IgM λ和未免疫的同类小鼠（B.A. 20)的 在IgH基因座上不同。 我们将进一步发展这两个模型系统， 研究肿瘤休眠

BCL1 leukemia is the first B cell leukemia to be described in mice having arisen spontaneously in an elderly BALB/c mouse. One cell transferred to a syngeneic recipient causes progressive leukemia that is always detectable by 12 weeks and is followed by progressive tumor growth and death. Mice rendered chimeric at the H-2 locus by lethal X-irradiation followed by injection of T cell depleted allogeneic bone marrow allow progressive growth of subsequently injected BCL1 cells. However, after 6 weeks, the tumor recedes and the mice appear tumor-free as judged by idiotype analysis of blood cells, white blood count, and spleen size. Disease does not occur for as long as the mice have been followed (8 months). Nevertheless, cell transfer studies indicate a relatively large tumor load in the spleen (10-6 - 10-7 cells). We will study the biology of tumor dormancy in attempts to answer the following questions: 1) What is the cell cycle status of the dormant cells? 2) Are they different from the starting population as judged by immunophenotype, response to lymphokines and karyotype? 3) What are the host defense mechanisms that are required to induce dormancy? 4) What is the natural history of dormancy, e.g. do dormant BCL1 cells eventually die or do they begin to grow when immune responsiveness decreases with age? 5) What perturbations can initiate tumor growth? 6) Can immunotoxins specific to BCL1 eliminate this dormant population in vivo? With regard to a syngeneic model of tumor dormancy, immunity to the BCL1 tumor has been generated in both BALB/c mice previously immunized with purified BCL1-IgMlambda and in non-immunized congenic mice (B.A. 20) that differ at the IgH locus. We will further develop these 2 model systems to study tumor dormancy.