DNA Topoisomerase IIa in Multiple Myeloma: A Marker of Cell Proliferation and Not Drug Resistance

DNA topoisomerase IIa (topo IIa) is the target for a number of antineoplastic agents. Down-regulation of this enzyme is one form of drug resistance. Topo IIa is also involved in DNA replication and transcription and serves as an indicator of proliferation rate in many human malignancies. This study examines whether topo IIa is one of the mechanisms of chemoresistance commonly observed in multiple myeloma (MM) or alternatively, whether topo IIa is associated with tumor cell proliferation. Bone marrow (BM) biopsy sections from 72 cases of MM, stratified according to proliferative activity (bromodeoxyuridine uptake), were immunostained for topo IIa. Immunoreactivity with an addi- tional marker of drug resistance, glutathione-S-transferase p, and the proliferation marker Ki-67 were also examined. Topo IIa was expressed in 26 (36%) cases and correlated strongly with proliferative activity (P