REVIEW: Mechanisms of Secondary Leukemia Development Caused by Treatment with DNA Topoisomerase Inhibitors

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Nikolai A. Lomov^1,a*, Vladimir S. Viushkov¹, and Mikhail A. Rubtsov^1,2

¹Department of Molecular Biology, Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia

²Department of Biochemistry, Center for Industrial Technologies and Entrepreneurship Sechenov First Moscow State Medical University (Sechenov University), 119435 Moscow, Russia

^* To whom correspondence should be addressed.

Received February 6, 2023; Revised April 14, 2023; Accepted April 20, 2023

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Leukemia is a blood cancer originating in the blood and bone marrow. Therapy-related leukemia is associated with prior chemotherapy. Although cancer therapy with DNA topoisomerase II inhibitors is one of the most effective cancer treatments, its side effects include development of secondary leukemia characterized by the chromosomal rearrangements affecting AML1 or MLL genes. Recurrent chromosomal translocations in the therapy-related leukemia differ from chromosomal rearrangements associated with other neoplasias. Here, we reviewed the factors that drive chromosomal translocations induced by cancer treatment with DNA topoisomerase II inhibitors, such as mobility of ends of double-strand DNA breaks formed before the translocation and gain of function of fusion proteins generated as a result of translocation.

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KEY WORDS: leukemia, translocations, fusion proteins, DNA topoisomerase II inhibitors

DOI: 10.1134/S0006297923070040

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