DEVELOPMENT OF LYMPHOMA IN THE THYMUS

这项建议的目的是描述白血病起源的特征 生长因子(LDGF)，一种自我刺激的生长因子，具有 从小鼠T淋巴瘤细胞中纯化至均一 是符合宪法规定的。有人建议，取消对 这种12,000 mW的糖蛋白生长因子导致了 胸腺的淋巴瘤。用放射性标记LDGF进行结合试验 将被开发用于识别不同靶点上的LDGF受体 细胞。低密度脂蛋白生长因子与正常淋巴细胞生理的关系 将使用胸腺细胞亚群和B淋巴母细胞来定义 台词。低密度脂蛋白生长因子在癌基因表达诱导中的作用 对于T淋巴瘤和对LDGF有反应的正常细胞将进行评估。 开发的提纯方法提供了足够的量 用于氨基酸测序的蛋白质。这一步将允许 用于抗体制备的多肽的合成。特异性抗体 将被用来开发一种放射免疫分析。抗体将检测 该分子在不同细胞群中的表达。抗体 将研究对LDGF刺激的细胞生长的影响。 寡核苷酸将从纯化的氨基酸中制备出来 序列鉴定编码低密度脂蛋白生长因子的cDNA克隆。高密度的细胞 将使用结合研究中确定的受体数量 纯化LDGF受体蛋白。 LDGF的特性和对其功能的理解 重要的原因有两个：1)人们对这些因素知之甚少 调节胸腺细胞的发育。LDGF可能就是这样一个因素； 2)自刺激性生长因子的结构性生产 如LDGF可能对这些组织的独立增长至关重要 细胞。因此，对这一因素的调查将增加 对正常淋巴系的生长和分化的认识 细胞，并可能为早期诊断和治疗提供新的途径 白血病的治疗。

The objective of this proposal is to characterize leukemia derived growth factor (LDGF), an autostimulatory growth factor which has been purified to homogeneity from murine T lymphoma cells where it is expressed constitutively. It is proposed that disregulation of this 12,000 MW glycoprotein growth factor leads to development of lymphoma in the thymus. A binding assay using radiolabeled LDGF will be developed to identify LDGF receptor on various target cells. The relationship of LDGF to normal lymphocyte physiology will be defined using thymocyte subpopulations and B lymphoblast lines. The role of LDGF in the induction of oncogene expression in T lymphomas and LDGF-responsive normal cells will be evaluated. The purification method developed provides sufficient quantities of protein for amino acid sequencing. This step will allow the synthesis of peptides for antibody preparation. Specific antibody will be used to develop a radioimmunoassay. Antibodies will test expression of the molecule in various cell populations. Antibody effect on LDGF-stimulated cell growth will be studied. Oligonucleotides will be prepared from a purified amino acid sequence to identify a cDNA clone encoding LDGF. Cells with high receptor numbers as determined in the binding studies will be used to purify the LDGF receptor protein. Characterization of LDGF and understanding of its the functions are important for two reasons: 1) there is little known about factors regulating about thymocyte development. LDGF may be such a factor; 2) the constitutive production of auto-stimulatory growth factors such as LDGF may be crucial to the independent growth of these cells. Therefore, investigation of this factor will add to knowledge of the growth and differentiation of normal lymphoid cells and may provide new approaches for early diagnosis and treatment of leukemia.