Absence of topoisomerase II beta in an amsacrine-resistant human leukemia cell line with mutant topoisomerase II alpha

Numerous chemotherapeutic agents act via stabilization of a topoisomerase ( topo) LI-DNA complex. HL-60/AMSA, a human leukemia cell line, is resistant to intercalator-mediated DNA complex formation and cytotoxicity, HL-60/AMSA contains a mutant form of topo Lieu that was thought to explain this resis tance. However, our present data show that expression of topo II beta RNA i n HL-60/AMSA is only 10% of that in HL-60, and topo II beta protein Levels are undetectable. Southern analysis of topo II beta shows no differences in gene dosage between the two cell lines but does show differences in the re striction patterns. These data suggest that decreased topo II beta expressi on may contribute to the intercalator resistance of HL-60/AMSA cells.