Mechanism of generation of therapy related leukemia in response to anti-topoisomerase II agents

Int J Environ Res Public Health. 2012 Jun;9(6):2075-91. doi: 10.3390/ijerph9062075. Epub 2012 May 31.


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.

Keywords: AML; TOP2; carcinogen; epirubicin; etoposide; leukemia; mitoxantrone; topoisomerase II; transcription; translocation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Humans
  • Leukemia, Myeloid, Acute / chemically induced*
  • Topoisomerase II Inhibitors / adverse effects*
  • Translocation, Genetic / drug effects


  • Topoisomerase II Inhibitors