Ultrastructural aspects of colchicine ultrasensitivity in CLL lymphocytes

Circulating lymphocytes from patients with chronic lymphatic leukaemia show extreme sensitivity to colchicine, with 80%-90% cell death after exposure to 10(-7) M colchicine for 20 h in vitro. This is 100,000-times greater than the dose required (10(-2) M) for a similarly toxic effect on normal lymphocytes. A time course series of fixations during the 20-h exposure of chronic lymphoid leukaemia (CLL) lymphocytes to 10(-7) colchicine revealed an entire spectrum of ultrastructural alterations well in advance of any sign of cell death, previously only ascertained by nuclear pycnosis in the light microscope. The changes included the appearance of large numbers of intermediate filaments, loss of surface microvilli, mitochondrial alterations and the formation of annulate lamellae. Mitochondrial changes included disruption of the cristae, swelling and tight clumping of the entire mitochondrial population into a single region of the cytoplasm.