Our objective is to prepare monoclonal antibodies which recognize the antigens expressed by normal or acute nonlymphocytic leukemic (ANL) progenitor cells. We will then use these antibodies to isolate and characterize normal progenitor subpopulations and determine if malignant progenitor cells can be separated from those capable of normal hematopoiesis. Our approach is based on our previous characterization of antigens present on normal myeloid colony forming cells and their precursors, including progenitors capable of establishing hematopoiesis in vivo. These antigenic markers were useful for distinguishing leukemic colony-forming cells from normal colony- forming cell precursors in some but not all patients with ANL. 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 proposal we will 1) prepare monoclonal antibodies that recognize novel antigens on normal and malignant progenitor cells, and define the biochemical nature of these antigens. We will then 2) use these antibodies to isolate and characterize normal and malignant progenitors present in ANL specimens that express a clonal marker. This will include studies to detect premalignant progenitors, and with patients in remission, rare populations of clonally derived cells. Selective depletion of ANL progenitor cells or isolation of normal progenitors would provide a rational basis for monoclonal antibody treatment of ANL.
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