Model of Metnase mediating resistance to Topo IIα inhibitors in AML. Topo IIα inhibitors are common in the clinical management of AML during salvage therapy. Metnase expression has been shown here to mediate resistance to VP-16. When Metnase is present in AML cells, it is able to interact with Topo IIα, enhancing its function and results in proper chromosomal decatenation during metaphase. In the case where Metnase is deficient, the presence of VP-16 reduces Topo IIα activity and cells are not able to decatenate sister chromatids, which results in metaphase arrest.