PLASMACYTOMAGENESIS AND LYMPHOCYTE DEVELOPMENT

一、白介素6(IL-6)已被证明是主要的增长 小鼠浆细胞瘤和人浆细胞瘤发生发展的相关因素 骨髓瘤。IL-6基因失活的小鼠具有抵抗力 对肿瘤的诱导，如肿瘤未能发展所证明的 在用含有raf和myc癌基因的逆转录病毒治疗后。 然而，当RAF被ABL取代时，这些小鼠会发展成肿瘤， 提示IL-6非依赖性肿瘤可以通过以下两种途径产生 其他癌基因组合或突变。我们已经研究了 细胞因子非依赖性肿瘤的发生机制 IL-6信号转导途径分析。白介素6与细胞因子的结合 其受体导致蛋白质级联反应的激活，从而导致 诱导新的基因表达和细胞生长。少校 在这个级联中的转录激活因子，命名为STAT 3，是 化学药物或癌基因诱发浆细胞肿瘤的评价 包括RAF/myc和ABL/myc。结果表明，IL-6途径 在化学肿瘤和RAF/myc肿瘤中是可诱导的，但是结构性的 被ABL/myc激活的STAT3被证明是在 细胞因子的存在或缺失。本构活化 可能是一种通用的机制，通过它许多 癌基因会破坏正常的细胞生长调节。 二、人类模型的开发研究仍在继续 用小鼠浆细胞瘤评价骨髓瘤的基因治疗 疾病治疗的方法。白介素2简介 (IL-2)基因导入浆细胞系可导致不同程度的 再次移植后与单个肿瘤相关的排斥反应 变成了动物。最近的实验使用辐射后的IL-2分泌 Cells在下面的2/2行中显示出显著的保护程度 挑战亲本细胞表明这些细胞可能是 有效地产生抗肿瘤反应，能够诱导 肿瘤排斥反应。

I. Interleukin-6 (IL-6) has been demonstrated to be the major growth factor involved in development of murine plasma cell tumors and human myeloma. Mice in which the IL-6 gene has been inactivated are resistant to tumor induction as evidenced by the failure of tumors to develop following treatment with retroviruses containing raf and myc oncogenes. However, these mice develop tumors when raf is replaced by abl, suggesting that IL-6 independent tumors can be generated either by other oncogene combinations or mutations. We have examined the mechanism by which cytokine independent tumors arise through an analysis of the IL-6 signal transduction pathway. Binding of IL-6 to its receptor leads to activation of a protein cascade resulting in induction of new gene expression and cell growth. The major transcription activating factor in this cascade, designated STAT 3, was evaluated in plasma cell tumors induced by chemical agents or oncogenes including raf/myc and abl/myc. Results indicate that the IL-6 pathway is inducible in chemical and raf/myc tumors, but constitutively activated by abl/myc as evidenced by phosphorylation of STAT 3 in either the presence or absence of cytokine. The constitutive activation of cytokine signaling pathways may be a general mechanism by which many oncogenes subvert normal cell growth regulation. II. Studies have continued on the development of a model for human myeloma using mouse plasma cell tumors to evaluate gene therapy approaches to disease treatment. Introduction of the Interleukin-2 (IL-2) gene into plasma cell lines results in varying degrees of rejection associated with individual tumors following re-introduction into animals. Recent experiments employing irradiated, IL-2 secreting cells reveals a significant degree of protection in 2/2 lines following challenge with parental cells suggesting that these cells may be effective in generating an anti-tumor response capable of inducing tumor rejection.