The object of this project is to analyze in depth the expression of regulatory phenotypes of normal and leukemic human progenitor cells, to correlate regulatory phenotype with the growth behavior of progenitor cells in vitro, and to define mechanisms for altering abnormal phenotypes in order to modify abnormal cell differentiation. A unique limited suspension culture system with prostaglandin E?1? (PGE?1?) will be used to modulate CFU-GM HLA-DR expression and investigate its implication in the control of CFU-GFM proliferation. A multifaceted in-depth study of specific modulation of antigenic expression and regulatory responsiveness in a strategy designed to restore a normal pattern of proliferation and differentiation offers a mechanism for control of leukemic cell proliferation and suggests an alternative approach to therapy. Evidence indicates that the disordered regulation observed in patients with CML can be restored by modulation of CFU-GM Ia-antigen following exposure to PGE. Analysis of normal, accessory cell function indicates a role for T lymphocytes in the control of CFU-GM cell cycle and Ia antigen expression. The mechanism(s) of action of T cells in normal and abnormal human myelopoiesis will be investigated. (MB)
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