Topotecan-induced topoisomerase IIalpha expression increases the sensitivity of the CML cell line K562 to subsequent etoposide plus mitoxantrone treatment.

Purpose: A new chemotherapy regimen was designed for leukemia to improve response to therapy and elucidate the possible underlying mechanisms responsible for its efficacy.

Methods: Cells of the chronic myelogenous leukemia (CML) cell line, K562, were treated singly, in combination, and in sequence with clinically equivalent dosages of topotecan, which targets topoisomerase I (Topo I), and etoposide and mitoxantrone, which target topoisomerase II (Topo II), to determine the best treatment. Apoptosis, early cell deaths, and cell cytotoxicities in drug-treated cells were determined with annexin V and propidium iodide staining and MTT assays, respectively.