Absence of topoisomerase IIbeta in an amsacrine-resistant human leukemia cell line with mutant topoisomerase IIalpha.

Numerous chemotherapeutic agents act via stabilization of a topoisomerase (topo) II-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 IIalpha that was thought to explain this resistance. However, our present data show that expression of topo IIbeta RNA in HL-60/AMSA is only 10% of that in HL-60, and topo IIbeta protein levels are undetectable. Southern analysis of topo IIbeta shows no differences in gene dosage between the two cell lines but does show differences in the restriction patterns. These data suggest that decreased topo IIbeta expression may contribute to the intercalator resistance of HL-60/AMSA cells.