Open Access
International Journal of Molecular Sciences, volume 23, issue 17, pages 9824
Recurrent Translocations in Topoisomerase Inhibitor-Related Leukemia Are Determined by the Features of DNA Breaks Rather Than by the Proximity of the Translocating Genes
Lomov Nikolai A
1
,
Viushkov Vladimir S
1
,
Ulianov Sergey V
1, 2
,
Gavrilov Alexey A
2
,
Alexeyevsky Daniil A
3
,
Artemov Artem V.
4
,
Razin Sergey V
1, 2
,
Rubtsov Mikhail I
1, 5
Publication type: Journal Article
Publication date: 2022-08-29
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor: 5.6
ISSN: 16616596, 14220067
PubMed ID:
36077220
Catalysis
Organic Chemistry
Inorganic Chemistry
Physical and Theoretical Chemistry
Computer Science Applications
Spectroscopy
Molecular Biology
General Medicine
Abstract
Topoisomerase inhibitors are widely used in cancer chemotherapy. However, one of the potential long-term adverse effects of such therapy is acute leukemia. A key feature of such therapy-induced acute myeloid leukemia (t-AML) is recurrent chromosomal translocations involving AML1 (RUNX1) or MLL (KMT2A) genes. The formation of chromosomal translocation depends on the spatial proximity of translocation partners and the mobility of the DNA ends. It is unclear which of these two factors might be decisive for recurrent t-AML translocations. Here, we used fluorescence in situ hybridization (FISH) and chromosome conformation capture followed by sequencing (4C-seq) to investigate double-strand DNA break formation and the mobility of broken ends upon etoposide treatment, as well as contacts between translocation partner genes. We detected the separation of the parts of the broken AML1 gene, as well as the increased mobility of these separated parts. 4C-seq analysis showed no evident contacts of AML1 and MLL with loci, implicated in recurrent t-AML translocations, either before or after etoposide treatment. We suggest that separation of the break ends and their increased non-targeted mobility—but not spatial predisposition of the rearrangement partners—plays a major role in the formation of these translocations.
Citations by journals
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Biochemistry (Moscow)
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Biochemistry (Moscow)
1 publication, 50%
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1
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Citations by publishers
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Pleiades Publishing
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Pleiades Publishing
1 publication, 50%
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1
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Lomov N. A. et al. Recurrent Translocations in Topoisomerase Inhibitor-Related Leukemia Are Determined by the Features of DNA Breaks Rather Than by the Proximity of the Translocating Genes // International Journal of Molecular Sciences. 2022. Vol. 23. No. 17. p. 9824.
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Lomov N. A., Viushkov V. S., Ulianov S. V., Gavrilov A. A., Alexeyevsky D. A., Artemov A. V., Razin S. V., Rubtsov M. I. Recurrent Translocations in Topoisomerase Inhibitor-Related Leukemia Are Determined by the Features of DNA Breaks Rather Than by the Proximity of the Translocating Genes // International Journal of Molecular Sciences. 2022. Vol. 23. No. 17. p. 9824.
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TY - JOUR
DO - 10.3390/ijms23179824
UR - https://doi.org/10.3390%2Fijms23179824
TI - Recurrent Translocations in Topoisomerase Inhibitor-Related Leukemia Are Determined by the Features of DNA Breaks Rather Than by the Proximity of the Translocating Genes
T2 - International Journal of Molecular Sciences
AU - Viushkov, Vladimir S
AU - Ulianov, Sergey V
AU - Gavrilov, Alexey A
AU - Alexeyevsky, Daniil A
AU - Artemov, Artem V.
AU - Razin, Sergey V
AU - Lomov, Nikolai A
AU - Rubtsov, Mikhail I
PY - 2022
DA - 2022/08/29 00:00:00
PB - Multidisciplinary Digital Publishing Institute (MDPI)
SP - 9824
IS - 17
VL - 23
PMID - 36077220
SN - 1661-6596
SN - 1422-0067
ER -
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BibTex
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@article{2022_Lomov,
author = {Vladimir S Viushkov and Sergey V Ulianov and Alexey A Gavrilov and Daniil A Alexeyevsky and Artem V. Artemov and Sergey V Razin and Nikolai A Lomov and Mikhail I Rubtsov},
title = {Recurrent Translocations in Topoisomerase Inhibitor-Related Leukemia Are Determined by the Features of DNA Breaks Rather Than by the Proximity of the Translocating Genes},
journal = {International Journal of Molecular Sciences},
year = {2022},
volume = {23},
publisher = {Multidisciplinary Digital Publishing Institute (MDPI)},
month = {aug},
url = {https://doi.org/10.3390%2Fijms23179824},
number = {17},
pages = {9824},
doi = {10.3390/ijms23179824}
}
Cite this
MLA
Copy
Lomov, Nikolai A., et al. “Recurrent Translocations in Topoisomerase Inhibitor-Related Leukemia Are Determined by the Features of DNA Breaks Rather Than by the Proximity of the Translocating Genes.” International Journal of Molecular Sciences, vol. 23, no. 17, Aug. 2022, p. 9824. https://doi.org/10.3390%2Fijms23179824.
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