Our objective is to prepare monoclonal antibodies that recognize the antigens expressed by acute nonlymphocytic leukemic (ANL) colony-forming cells. We will then use these antibodies to separate malignant progenitor cells from those capable of normal hematopoiesis. Success in these studies may lead to the development of new methods of treating ANL. Our approach is based on our previous development of monoclonal antibodies that recognize normal myeloid stem cells and their progeny at distinct stages of differentiation. These monoclonal antibodies were able to deplete leukemic colony-forming cells from patients with ANL without completely eliminating normal stem cells. An important aspect of these studies was the use of a clonal marker to discern the malignant versus normal origin of the separated stem cell populations. In the period of this research we will: (1) produce monoclonal antibodies capable of lysing malignant colony-forming cells; (2) examine the cellular and biochemical specificity of these antibodies; (3) determine the antigenic phenotype and differentiative capacity of the malignant colony-forming cells; and (4) use these antibodies to lyse colony-forming cells present in ANL specimens that express a clonal marker. Under these conditions we can test whether the colony-forming cells remaining after lysis are predominantly derived from the leukemic clone or are of nonclonal, presumably normal, origin. This selective depletion of ANL progenitor cells would provide a rational basis for monoclonal antibody treatment of ANL. (MI)
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