PMID- 36077220
OWN - NLM
STAT- MEDLINE
DCOM- 20220912
LR  - 20220913
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 23
IP  - 17
DP  - 2022 Aug 29
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.
LID - 10.3390/ijms23179824 [doi]
LID - 9824
AB  - 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.
FAU - Lomov, Nikolai A
AU  - Lomov NA
AUID- ORCID: 0000-0003-2101-3479
AD  - Department of Molecular Biology, Faculty of Biology, Lomonosov Moscow State 
      University, Moscow 119234, Russia.
FAU - Viushkov, Vladimir S
AU  - Viushkov VS
AD  - Department of Molecular Biology, Faculty of Biology, Lomonosov Moscow State 
      University, Moscow 119234, Russia.
FAU - Ulianov, Sergey V
AU  - Ulianov SV
AD  - Department of Molecular Biology, Faculty of Biology, Lomonosov Moscow State 
      University, Moscow 119234, Russia.
AD  - Institute of Gene Biology, Russian Academy of Sciences, Moscow 119334, Russia.
FAU - Gavrilov, Alexey A
AU  - Gavrilov AA
AD  - Institute of Gene Biology, Russian Academy of Sciences, Moscow 119334, Russia.
FAU - Alexeyevsky, Daniil A
AU  - Alexeyevsky DA
AD  - A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State 
      University, Moscow 119234, Russia.
FAU - Artemov, Artem V
AU  - Artemov AV
AD  - Department of Neuroimmunology, Center for Brain Research, Medical University of 
      Vienna, 1090 Vienna, Austria.
FAU - Razin, Sergey V
AU  - Razin SV
AD  - Department of Molecular Biology, Faculty of Biology, Lomonosov Moscow State 
      University, Moscow 119234, Russia.
AD  - Institute of Gene Biology, Russian Academy of Sciences, Moscow 119334, Russia.
FAU - Rubtsov, Mikhail A
AU  - Rubtsov MA
AUID- ORCID: 0000-0003-4947-1009
AD  - Department of Molecular Biology, Faculty of Biology, Lomonosov Moscow State 
      University, Moscow 119234, Russia.
AD  - Department of Biochemistry, Center for Industrial Technologies and 
      Entrepreneurship I.M., Sechenov First Moscow State Medical University (Sechenov 
      University), Moscow 119435, Russia.
LA  - eng
GR  - 19-04-00531_A/Russian Foundation for Basic Research/
GR  - 075-15-2021-1062/Ministry of Science and Higher Education of the Russian 
      Federation/
PT  - Journal Article
DEP - 20220829
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Topoisomerase II Inhibitors)
RN  - 6PLQ3CP4P3 (Etoposide)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - DNA
MH  - DNA Breaks, Double-Stranded
MH  - Etoposide/adverse effects
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - *Leukemia, Myeloid, Acute/genetics
MH  - Topoisomerase II Inhibitors/adverse effects
MH  - *Translocation, Genetic
PMC - PMC9456246
OTO - NOTNLM
OT  - AML1
OT  - KMT2A
OT  - MLL
OT  - RUNX1
OT  - chromosomal translocation
OT  - etoposide
OT  - t-AML
OT  - therapy-related AML
OT  - topoisomerase inhibitor-related leukemia
OT  - topoisomerase inhibitors
COIS- The authors declare no conflict of interest.
EDAT- 2022/09/10 06:00
MHDA- 2022/09/14 06:00
PMCR- 2022/08/29
CRDT- 2022/09/09 01:07
PHST- 2022/06/25 00:00 [received]
PHST- 2022/08/09 00:00 [revised]
PHST- 2022/08/21 00:00 [accepted]
PHST- 2022/09/09 01:07 [entrez]
PHST- 2022/09/10 06:00 [pubmed]
PHST- 2022/09/14 06:00 [medline]
PHST- 2022/08/29 00:00 [pmc-release]
AID - ijms23179824 [pii]
AID - ijms-23-09824 [pii]
AID - 10.3390/ijms23179824 [doi]
PST - epublish
SO  - Int J Mol Sci. 2022 Aug 29;23(17):9824. doi: 10.3390/ijms23179824.