Characterization of human acute myeloid leukemia progenitor cells: growth factor responsiveness and membrane phenotype.

Blood cell formation takes place Multipotential bone marrow stem cells primarily in the bone marrow. are able to undergo selfrenewal or produce progenitor cells which are predestinated to mature towards certain functional blood cells, e.g. erythrocytes, granulocytes, monocytes, platelets or lymphocytes. The process of blood cell production is regulated by hematopoietic growth factors (HGFs). In the past two decades culture systems have been developed, which enabled the study of the role of HGFs in the proliferation and maturation of bone marrow progenitor cells in vitro. When appropriately stimulated the different progenitor cells give rise to colonies containing mature cells. In acute myeloid leukemia (AML), myelomonocytic cells are arrested at an early stage of maturation (blasts) and accumulate in the marrow and in the blood. AML blasts may be cultured in vitro as well. AML colony forming cells (AML-CFU) give rise to colonies containing leukemic blast cells. Normal bone marrow colony forming cells can be identified among other hematopoietic cells using monoclonal antibodies directed towards membrane antigens and with immunologic cell separation procedures. using the same techniques, AML-CFUs can also be recognized as distinct subpopulations of cells with membrane surface characteristics different from those of nonclonogenic AML cells. one of the objectives of the investigations presented in this thesis was to search for differences in surface marker expression between AYlli-CFU and normal bone marrow progenitor cells. Such dissimilarities could be of use in the diagnosis of AML, in particular for the detection of minimal numbers of AML progenitor cells in remission marrow (following chemotherapy or bone marrow transplantation).