DEVELOPMENT OF LYMPHOMA IN THE THYMUS

该提案的目的是描述白血病衍生的 生长因子（LDGF），一种自身刺激生长因子， 从鼠T淋巴瘤细胞中纯化至同质， 是由宪法规定的。 有人建议， 这种分子量为12，000的糖蛋白生长因子导致 胸腺淋巴瘤 使用放射性标记的LDGF的结合测定 将开发用于鉴定各种靶点上的LDGF受体 细胞 LDGF与正常淋巴细胞生理的关系 将使用胸腺细胞亚群和B淋巴母细胞定义 线 LDGF诱导癌基因表达的作用 在T淋巴瘤和LDGF-反应性正常细胞中进行评价。 开发的纯化方法提供了足够的量 用于氨基酸测序。 此步骤将允许 用于抗体制备的肽的合成。 特异性抗体 将用于开发放射免疫分析。 抗体将测试 该分子在各种细胞群体中的表达。 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制备 序列以鉴定编码LDGF的cDNA克隆。 细胞高 将使用结合研究中确定的受体数量 纯化LDGF受体蛋白。 LDGF的特性及其功能的理解是 重要的原因有两个：1）对因素知之甚少 调节胸腺细胞的发育。 LDGF可能是这样一个因素; 2)自身刺激生长因子的组成性生产 例如LDGF可能对这些国家的独立增长至关重要， 细胞 因此，对这一因素的调查将增加 了解正常淋巴细胞的生长和分化 细胞，并可能为早期诊断提供新的方法， 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.