Proliferation and differentiation of normal and chronic myeloid leukaemia (CML) marrow cells in suspension cultures.

Immature myeloid cells highly enriched for colony-forming cells, myeloblasts and promyelocytes were isolated in Percoll gradients (lighter than 1.065 g/ml) from patients with chronic myeloid leukaemia (CML) or normal healthy volunteers. The proliferation and differentiation of these cells were followed in suspension cultures in McCoy's medium (15% FCS) with or without the addition of 15% human placenta conditioned medium (HP-CM) over a culture period of 12-16 d. Ion-exchange chromatography and gel chromatography indicated that the proliferation-stimulating activity in HP-CM was colony-stimulating activity (CSA). In unstimulated cultures (without HP-CM), normal cells produced very few neutrophils; macrophage production dominated. CML cells, on the other hand, gave rise to neutrophils even in the absence of stimulatory factor(s). The effect of HP-CM was dependent on the initial concentration: at a 'low' (1 X 10(5)/ml) concentration, the addition of HP-CM resulted in a great increase in neutrophils, but at a 'high' (5-8 X 10(5)/ml) initial cell concentration, HP-CM gave only minimal increase in neutrophil numbers in both normal and CML cultures. These observations suggest endogenous differences between normal and CML precursors in their requirements for or responses to growth stimulatory or inhibitory factors.