More successful therapy of hematologic disorders including malignancies requires increased information concerning the processes involved in normal hematopoietic differentiation. A major long-term goal of this work is to understand the critical early events in normal human hematopoiesis which occur as a cell """"""""decides"""""""" between self-renewal and lineage committment and as a cell matures along a lineage pathway. Direct experiments in this area require purified hematopoietic progenitor cells, and therefore would be enabled by a comprehensive battery of monoclonal antibodies recognizing antigens expressed specifically on early hematopoietic cell types. The epitope detected by the anti-My-10 monoclonal antibody is expressed specifically on human marrow blast cells, including essentially all measured hematopoietic progenitor cells. In part I of this project, monospecific rabbit antisera will be prepared against the purified My-10 glycoprotein, in order to determine whether expression of the entire My-10 glycoprotein is restricted to early hematopoietic developmental stages. Additional monoclonal antibodies against the My-10 glycoprotein will also be produced, to allow improved labelling and isolation of My-10- positive marrow progenitor cells. Methods for affinity purification of My-10-positive cells will be tested, as feasibility studies prior to a clinical trial of the use of purified My-10- positive """"""""stem cells"""""""" for clinical bone marrow transplantation with a reduced risk of Graft versus Host Disease. Novel specific anti-human hematopoietic progenitor cell monoclonal antibodies will also be generated in this project and will be used in analysis and isolation of hematopoietic progenitor cells. The second major specific goal of this project is the use of these and other available monoclonal antibodies, with flow cytometry, to construct detailed """"""""maps"""""""" of normal hematopoietic cellular development. These maps will be used to investigate the cellular events in normal versus abnormal myeloid cell.
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