Hodgkin's disease is a unique lymphoma in which the neoplastic cells (Hodgkin's-Reed-Sternberg or H-RS cells) often constribute less than 5% of the total cells in the involved lymphoid tissues. However, the tissues are characterized by the presence of abundant reactive cells, such as T and B lymphocytes, histiocytes, eosinophils, and fibroblasts. Recently, we have observed that the H-RS cell line HDLM-1 can produce a macrophage-differentiating factor that induces the histiocytic differentiation of a promyelocytic cell line, ML-1, and promotes macrophage colony formation in cultured bone marrow cells. Functional and biochemical studies of this cytokine indicate that the HDLM-1- derived macrophage-differentiating factor is distinct from presently known colony-stimulating factors, interleukins, and interferons. In the study proposed here, we intend to characterize this macrophage-differentiating factor further in detail.
The aims of this study are as follows: (1) To characterize and purify the macrophage-differentiating factor; (2) compare the macrophage-differentiating factor with other, possibly related cytokines, growth factors, or oncogenes; (3) produce monoclonal antibodies or antiserum against the macrophage-differentiating factor; (4) isolate and characterize the gene encoding the macrophage-differentiating factor from the HDLM-1 cDNA bank; (5) explore the biological function of the HDLM-1-derived or recombinant macrophage-differentiating factor on normal monocytes/macrophages and assess its therapeutic potential on leukemia/lymphoma cells in culture. This study proposed in this grant application is feasible because the large-scale growth of neoplastic H-RS (HDLM-1) cells and the production of macrophage-differentiating factor for biochemical and biological studies are unlimited. Because the macrophage- differentiating factor can irreversibly commit the immature leukemia cells or the bone marrow progenitor cells to enter a differentiation pathway, this factor may have clinical value for the treatment of patients with myeloid/monocytoid leukemias. The study also is expected to provide information which should faciliate the understanding of the immunobiology of Hodgkin's disease.
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