Characteristics of vincristine resistance in vincristine resistant human myelogenous leukemia K562.

A stable vincristine (VCR)-resistant variant (K562/VCR) was established from human myelogenous leukemia K562 by continuous exposure of the cells with increasing concentration of VCR up to 30 nM, followed by the maintenance of the cells in the presence of 30 nM of VCR for 6 months. In four clones with different VCR sensitivity, the extent of VCR-resistance and Adriamycin-resistance was always parallel among the clones, indicating a tight relationship between VCR- and ADM-resistance mechanisms. The clones accumulated significantly low amounts of VCR in the cells. The amounts of VCR in the clones and K562/VCR were inversely related to the extent of resistance of the cells. The rate and the extent of VCR efflux from the cells were parallel to the extent of resistance of the cells to VCR. One VCR-resistant clone, KV-11, was found to possess diminished amounts of beta-tubulin.