A physiological factor, the maturation inducer (MI, m.w. 50,000), produced by T cells and capable of inducing the differentiation and maturation of human myeloid leukemia cells has been described. It has been demonstrated to be distinct from the commonly known lymphokines and may be the human counterpart of the murine differentiation factor MGI2 for myeloid leukemia cells. It has been demonstrated media in vitro and in vivo growth suppressioin and differentiation of leukemia cells. With the available MI molecules and specific monoclonal antibodies, we plan to investigate the differentiation blocks and defects in leukemia, and to evaluate differentiation indunction as a corrective approach. The quantitation of serum MI level in leukemia patients and normal persons will be compared by an ELISA method using antibodies. An assessment will be made as to whether there is a lack of MI in patients. Immunofluorescent antibody techniques will be used to quantitate the MI producing lymphocytes. The level of producing cells in normal persons has been determined and an assessment can be made as to whether there is a lack of these cells in patients. Furthermore, cell-MI interactions will be studied by analyzing the number of membrane receptors and binding specificity. The effectivity of the interaction of leukemia cells with the MI will be revealed. Myeloid leukemia cells have been shown to be induced to differentiation normally by the maturation inducer, suggesting the use of MI stimulation of the production of MI in vivo, or the use of MI-producing cells as grafts. Patient lymphocytes will be cultured with IL2 to assess MI production and the growth of the producing cells as an autologous source. Large quantities of MI will be prepared by cell lines constitutively producing MI, and by T-T cell hybridomas, using affinity chromatography, etc. The proposed research will reveal the basis of leukogenesis and provide crucial information for corrective approaches.
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