Drug sensitivity and cross-resistance of the 4'-(9-acridinylamino)methanesulfon-m-anisidide-resistant subline of HL-60 human leukemia.

A subline of the HL-60 leukemia resistant to 4'-(9-acridinylamino)methanesulfon-m-anisidide (HL-60/AMSA) was developed by intermittent long-term in vitro treatment. Resistance to 4'-(9-acridinylamino)methanesulfon-m-anisidide remained unchanged after 180 doublings in the absence of the drug, suggesting a stable phenotypic alteration. The pattern of cross-resistance of HL-60/AMSA was evaluated for a spectrum of antileukemic agents using the clonogenic assay. Modest cross-resistance to doxorubicin (Adriamycin) was observed in the resistant subline on continuous exposure to the drug for 8 to 9 days; however, HL-60/AMSA cells retained their sensitivity to doxorubicin following short-term exposure for 60 min. HL-60/AMSA was also sensitive to the anthracycline aclacinomycin, Vinca alkaloids, and alkylating agents. Furthermore, enhanced sensitivity to 1-beta-D-arabinofuranosylcytosine was observed. The subline was cross-resistant to etoposide.