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Mechanism of Generation of Therapy Related Leukemia in Response to Anti-Topoisomerase II Agents

Lookup NU author(s): Dr Ian CowellORCiD, Emerita Professor Caroline AustinORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

Type II DNA topoisomerases have the ability to generate a transient DNA double-strand break through which a second duplex can be passed; an activity essential for DNA decatenation and unknotting. Topoisomerase poisons stabilize the normally transient topoisomerase-induced DSBs and are potent and widely used anticancer drugs. However, their use is associated with therapy-related secondary leukemia, often bearing 11q23 translocations involving the MLL gene. We will explain recent discoveries in the fields of topoisomerase biology and transcription that have consequences for our understanding of the etiology of leukemia, especially therapy-related secondary leukemia and describe how these findings may help minimize the occurrence of these neoplasias.

Publication metadata

Author(s): Cowell IG, Austin CA

Publication type: Review

Publication status: Published

Journal: International Journal of Environmental Research and Public Health

Year: 2012

Volume: 9

Issue: 6

Pages: 2075-2091

Print publication date: 31/05/2012

ISSN (print): 1661-7827

ISSN (electronic): 1660-4601

Publisher: MDPI AG

URL: http://dx.doi.org/10.3390/ijerph9062075

DOI: 10.3390/ijerph9062075

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