Restoration with phorbol ester of a locomotor defect in human leukaemic lymphocytes: a visual study of chronic lymphocytic leukaemia cells.

Visual assays were used to study the effect of phorbol myristate acetate (PMA) on the locomotion of lymphocytes from 14 patients with chronic lymphocytic leukaemia (CLL). Previous reports had shown that CLL cells from blood were defective in locomotor capacity and that adding PMA to the cells did not restore locomotion in a short-term (30 min) assay, but did stimulate unusual non-locomotor, multipolar, morphologies in a small proportion of the cells. Here we describe experiments in which CLL cells were cultured for 48 h in PMA. Many of the cells acquired locomotor morphologies with front-tail polarity which was unlike the short-term multipolar morphology. These cultured cells were also capable of locomotion and invaded collagen gels. Autoradiography suggested that after culture in PMA, the locomotory cells were the most active cells in 3H-uridine uptake. A computer analysis suggested that the cells in locomotor morphology were the same cells that increased in size. These findings suggest that, to acquire locomotor capacity, CLL lymphocytes require an appropriate signal to allow the cells to enter the cell cycle. During G1 the lymphocytes develop the capacity for locomotion. Long-term, but not short-term, culture in PMA provides such a signal but the mechanism by which it does so is unclear.