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Drug Sensitivity and Cross-Resistance of the 4'-(9-Acridinylamino)methanesulfon-m-anisidide-resistant Subline of HL-60 Human Leukemia

Department of Hematology, The University of Texas, M. D. Anderson Hospital and Tumor Institute at Houston, Houston, Texas 77030

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-ß-D-arabinofuranosylcytosine was observed. The subline was cross-resistant to etoposide.

¹ Special Fellow of the Leukemia Society of America, Inc.

² To whom requests for reprints should be addressed.

Received 10/ 2/85. Revised 1/ 9/86. Accepted 3/18/86.