Clone size potential and sensitivity to colony-stimulating activity: differentiation-linked properties of...

Previous studies using semi-solid agar cultures of acute myeloid leukaemia (AML) cells have shown that proliferative capacity (clone size potential) and the degree of sensitivity of clone-forming cells to the specific granulocyte-macrophage regulatory colony-stimulating activity (CSA) are closely linked AML cell properties. The purpose of this study was to determine whether this association is confined to AML cells or whether the linking of these two properties in AML represents retention of an association occurring in normal granulocyte-monocyte progenitor cell populations. Bone marrow cells from normal donors were studied using four independent techniques to enrich for clonogenic cells with different clone size potentials (equilibrium density centrifugation, adherence to microcarrier beads, osmotic lysis and fluorescence-activated cell sorting). It was shown that mean clone size was directly related to the mean CSA threshold (amount of CSA required to stimulate 50% of the cells to clone formation). Further studies (including analysis of the kinetics of production of clonogenic cells with different clone size potentials in suspension culture) suggested that these two properties were linked to differentiation, with proliferative capacity decreasing and sensitivity to CSA increasing as cells differentiate down the granulocyte-monocyte pathway.