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

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Abstract

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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Abbreviations

AML1 (or RUNX1):

acute myeloid leukemia-associated gene (RUNX family transcription factor 1)

DSB:

double-strand DNA break

ETO (or RUNX1T1):

RUNX1 partner transcriptional co-repressor 1; gene often rearranged with the formation of translocation t(8;21)

MLL (or KMT2A):

mixed phenotype leukemia-associated gene (lysin-specific methyltransferase 2A)

NHEJ:

non-homologous end joining

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Funding

The study was supported by the Ministry of Science and Higher Education of the Russian Federation (agreement no. 075-15-2021-1062) and the Interdisciplinary Research and Education School of Moscow State University “Molecular Technologies of Living Systems and Synthetic Biology”.

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Authors and Affiliations

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

    Nikolai A. Lomov, Vladimir S. Viushkov & Mikhail A. Rubtsov

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

    Mikhail A. Rubtsov

Authors
  1. Nikolai A. Lomov
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  2. Vladimir S. Viushkov
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  3. Mikhail A. Rubtsov
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All authors participated in writing this review.

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Correspondence to Nikolai A. Lomov.

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The authors declare no conflict of interest. This article does not contain description of studies with human participants or animals performed by any of the authors.

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Lomov, N.A., Viushkov, V.S. & Rubtsov, M.A. Mechanisms of Secondary Leukemia Development Caused by Treatment with DNA Topoisomerase Inhibitors. Biochemistry Moscow 88, 892–911 (2023). https://doi.org/10.1134/S0006297923070040

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  • DOI: https://doi.org/10.1134/S0006297923070040

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