PLASMACYTOMAGENESIS AND LYMPHOCYTE DEVELOPMENT

一、白介素6(IL-6)被认为是主要的细胞因子 与小鼠和小鼠浆细胞肿瘤的发展有关 人类。这一结论在很大程度上是基于体外研究，其中 许多小鼠浆细胞瘤和人类骨髓瘤株都被 显示依赖IL-6进行增殖。要解决这个问题 IL-6在浆细胞发育中的体内作用问题 肿瘤，我们使用了携带IL-6零突变的小鼠 基因，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 含有逆转录病毒的。含有逆转录病毒的MYC/RAF未能 空等位基因纯合子诱导小鼠浆细胞肿瘤的研究 表明完全依赖IL-6诱导肿瘤 这些致癌基因。相反，Abl/myc诱导小鼠体内浆细胞肿瘤 这些小鼠的发病率为50%，这表明一些突变 联合用药可能会诱发IL-6非依赖性肿瘤。这个 这两种表型的出现频率将在 确定首选的治疗方法。 II.检测了小鼠浆细胞瘤的转移潜能 试图建立一种人类多发性骨髓瘤模型，该模型 将在治疗方法的评估中使用。几个 已经确定了产生转移性疾病和 侵入骨髓，这是人类疾病的主要部位。细胞系 感染了表达白介素2基因的逆转录病毒 (IL-2)，然后注射到动物体内以评估发生 IL-2介导的肿瘤排斥反应。初步结果表明 同一类型肿瘤之间的差异有统计学意义 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.