Establishment and properties of vincristine-resistant human myelogenous leukemia K562.

A vincristine (VCR)-resistant subline of human K562 myelogenous leukemia was established in vitro, and several clones with different susceptibilities to VCR were isolated by the limiting dilution technique. The most resistant clone (H-1) had a 17-fold greater resistance to VCR when compared to the parent K562 cells. The clone gradually lost the resistance during prolonged culture in vitro. These clones generally accumulated smaller amounts of VCR in their cells as compared to the parent cells. The size of H-1 clone cells was almost the same as that of the parent cells. The numbers of potential binding sites of VCR in the K562 cells and the resistant H-1 clone were almost the same. Similar results were obtained for P388 and its VCR-resistant subline. The cells derived from the VCR-resistant H-1 clone were highly cross-resistant to vindesine and moderately resistant to vinblastine. Cells derived from clone H-1 exhibited marginal degrees of cross-resistance to adriamycin, maytansine and VP-16-213, whereas VCR-resistant P388 leukemia cells exhibited significant resistance to these agents, especially to maytansine.