DEVELOPMENT OF LYMPHOMA IN THE THYMUS

目的是表征白血病衍生生长因子（LDGF）， 自刺激生长因子已从 鼠T淋巴瘤细胞，其中其组成型表达。 是 提出这种分子量为12，000的糖蛋白生长因子的失调 导致胸腺淋巴瘤的发展。 结合试验， 将开发放射性标记的LDGF以鉴定各种细胞上的LDGF受体。 靶细胞 LDGF与正常淋巴细胞生理的关系 将使用胸腺细胞亚群和B淋巴母细胞系来定义。 LDGF诱导T淋巴瘤癌基因表达的作用及意义 将评价LDGF应答正常细胞。 纯化方法 开发提供足够数量的蛋白质的氨基酸 测序 这一步骤将允许合成用于抗体的肽 准备. 特异性抗体将用于开发一种 放射免疫法 抗体将测试分子的表达， 不同的细胞群体。 抗体对LDGF刺激的细胞生长的影响 将被研究。 寡核苷酸将从纯化的氨基 酸序列以鉴定编码LDGF的cDNA克隆。 细胞高 结合研究中确定的受体数量将用于 纯化LDGF受体蛋白。 LDGF的特性及其功能的理解是重要的 有两个原因：1）对调节的因素知之甚少 胸腺细胞发育 LDGF可能是这样一个因素; 2）组成型 自身刺激生长因子如LDGF的产生可能对 这些细胞的独立生长。 对这一因素的调查将 增加对正常淋巴细胞生长和分化的认识 并可能为早期诊断和治疗提供新的方法 白血病

The objective 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 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 autostimulatory growth factors such as LDGF may be crucial to the independent growth of these cells. 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.