
<ArticleTitle><prot>DNA topoisomerase IIalpha</prot> in multiple myeloma: a marker of cell proliferation and not drug resistance.</ArticleTitle>
<AbstractText><prot>DNA topoisomerase IIalpha</prot> (<prot>topo IIalpha</prot>) is the target for a number of antineoplastic agents. Down-regulation of this enzyme is one form of drug resistance. <prot>Topo IIalpha</prot> is also involved in DNA replication and transcription and serves as an indicator of proliferation rate in many human malignancies. This study examines whether <prot>topo IIalpha</prot> is one of the mechanisms of chemoresistance commonly observed in multiple myeloma (MM) or alternatively, whether <prot>topo IIalpha</prot> 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 <prot>topo IIalpha</prot>. Immunoreactivity with an additional marker of drug resistance, glutathione-S-transferase pi, and the proliferation marker Ki-67 were also examined. <prot>Topo IIalpha</prot> was expressed in 26 (36%) cases and correlated strongly with proliferative activity (P &#60;.001). A role for drug resistance could not be supported, given this strong relationship with proliferation and the finding that glutathione-S-transferase pi expression in 57 (78%) cases was independent of <prot>topo IIalpha</prot> immunoreactivity. <prot>Topo IIalpha</prot> was identified in 91 to 100% of highly proliferative tumors, as evaluated by bromodeoxyuridine uptake or Ki-67 reactivity, respectively. Proliferation also correlated with the histologic grade of the MM. Therefore, <prot>topo IIalpha</prot> immunoreactivity is primarily a marker of cell proliferation in MM and as such is likely to have prognostic significance. Highly proliferative tumors are most likely to be sensitive to chemotherapeutic protocols using anti-topo IIalpha agents.</AbstractText>
