DEVELOPMENT OF LYMPHOMA IN THE THYMUS

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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.