The Role of DNA Topoisomerase II in Multidrug Resistance in Human Leukemia
Resistance to chemotherapy continues to be a major impediment and intellectual challenge to the cure of neoplastic diseases, and leukemias are no exception. Resistance of tumor cells to multiple “natural product” anticancer drugs, known as multidrug resistance (MDR), is now a well-documented phenomenon, and some excellent reviews have recently summarized its pharmacology and cell and molecular biology [1–5]. It is now clear that several types of natural product MDR exist experimentally: one is associated with P-glycoprotein (Pgp) over-expression (Pgp-MDR) [1–5], another with alterations in DNA topoisomerase II (at-MDR) (reviewed in ), and a third with features similar to Pgp-MDR but without Pgp overexpression [7, 8]. Although PgpMDR appears to have clinical correlates, we do not yet know about the clinical relevance of other forms of MDR. In this chapter, we focus on at-MDR.
KeywordsLeukemia Resis Alkaloid Verapamil Cond
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