Proliferative capacity, sensitivity to colony stimulating activity and buoyant density: Linked properties of granulocyte-macrophage progenitors from normal human bone marrow

Abstract

Phenotypic differences between acute myeloid leukaemia (AML) cells and normal cells can only be attributed to abnormal AML cell properties if comparisons have been made with the precise normal counterpart cell. When AML clonogenic cells are compared with the normal bone marrow cells which form clones of granulocytes and macrophages in agar culture, differences are detected. These include lower average buoyant density and varying degrees of reduced sensitivity to the specific regulator granulocyte-macrophage colony stimulating activity (CSA). The degree of reduction in sensitivity to CSA is inversely related to the proliferative capacity of the individual's AML cells. This association suggests that the phenotypes of different AML cell populations might be a parody of the phenotypic heterogeneity of the normal granulocyte-monocyte progenitor population; heterogeneity which possibly reflects the maturation hierarchy of the normal population. The aim of this study was to test this thesis. The results show that buoyant density, proliferative capacity and sensitivity to CSA are heterogenous properties of normal granulocyte-monocyte progenitor cells which are linked in an orderly manner. Buoyant density and CSA sensitivity differences between AML cells and normal progenitor cells may thus indicate shifts in the location of the majority of progenitor cells on the granulocyte-monocyte pathway in AML rather than abnormal cell properties.