PLASMACYTOMAGENESIS AND LYMPHOCYTE DEVELOPMENT

I. 白细胞介素-6（IL-6）被认为是主要的细胞因子 参与小鼠浆细胞肿瘤的发展， 人类 这一结论主要基于体外研究， 许多鼠浆细胞瘤和人骨髓瘤细胞系已经被 显示其增殖依赖于IL-6。 解决 IL-6在浆细胞发育中的体内作用的问题 肿瘤，我们使用了携带IL-6无效突变的小鼠， 因此不能产生相应的细胞因子。 使用myc/raf或Abl/myc进行肿瘤诱导研究 含有逆转录病毒。 含Myc/Raf的逆转录病毒不能 在无效等位基因纯合子小鼠中诱导浆细胞肿瘤 表明肿瘤诱导完全依赖于IL-6， 这些致癌基因。 与此相反，Abl/myc诱导的浆细胞肿瘤在100例中， 这些相同的小鼠在50%的发病率表明，一些突变， 组合可能诱导IL-6非依赖性肿瘤。 的 这两种表型的出现频率在以下方面将是重要的： 定义优选的治疗方法。 二. 小鼠浆细胞瘤的转移潜能已经被研究 在建立人多发性骨髓瘤模型尝试中， 将用于评估治疗方法。 几 已经鉴定了产生转移性疾病的细胞系， 渗入骨髓，人类疾病的主要部位。 细胞系 感染了表达白细胞介素-2基因的逆转录病毒 （IL-2），随后注射到动物体内，以评估 IL-2介导的肿瘤排斥反应。 初步结果表明 同一类肿瘤之间的显著差异 诱导IL-2介导的排斥反应的能力。

I. Interleukin-6 (IL-6) has been suggested to be the major cytokine involved in the development of plasma cell tumors in both mice and humans. This conclusion is based largely on in vitro studies in which a number of both murine plasmacytoma and human myeloma lines have been shown to be dependent on IL-6 for proliferation. To address the question of the in vivo role of IL-6 in the development of plasma cell neoplasias, we have employed mice carrying a null mutation in the IL-6 gene and thus incapable of producing the corresponding cytokine. Tumor induction studies were conducted using myc/raf or Abl/myc containing retroviruses. Myc/raf containing retroviruses failed to induce plasma cell tumors in mice homozygous for the null allele indicating a complete dependence on IL-6 for tumor induction with these oncogenes. In contrast, Abl/myc induced plasma cell tumors in these same mice at an incidence of 50% indicating that some mutational combinations are likely to induce IL-6 independent tumors. The frequency of occurrence of these two phenotypes will be important in defining preferred therapeutic approaches. II. The metastatic potential of murine plasmacytoma has been examined in an attempt to establish a model for human multiple myeloma which will be of use in the evaluation of therapeutic approaches. Several lines have been identified which produce metastatic disease and infiltrate bone marrow, the primary site of human disease. Cell lines have been infected with retroviruses expressing the Interleukin-2 gene (IL-2) and subsequently injected into animals to assess the occurrence of IL-2 mediated tumor rejection. Initial results indicate significant differences among tumors of the same class in their abilities to induce IL-2 mediated rejection.