The urinary excretion of epigenetically modified DNA as a marker of pediatric ALL status and chemotherapy response

The urinary excretion of epigenetically modified DNA as a marker of pediatric ALL status and chemotherapy response

Abstract The active DNA demethylation process may be linked to aberrant methylation and may be involved in leukemogenesis. We investigated the role of epigenetic DNA modifications in childhood acute lymphoblastic leukemia (ALL) diagnostics and therapy monitoring. We analyzed the levels of 5-methyl-2...

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Autores principales: Rafal Rozalski, Daniel Gackowski, Aleksandra Skalska-Bugala, Marta Starczak, Agnieszka Siomek-Gorecka, Ewelina Zarakowska, Martyna Modrzejewska, Tomasz Dziaman, Anna Szpila, Kinga Linowiecka, Jolanta Guz, Justyna Szpotan, Maciej Gawronski, Anna Labejszo, Lidia Gackowska, Marek Foksinski, Elwira Olinska, Aleksandra Wasilow, Andrzej Koltan, Jan Styczynski, Ryszard Olinski
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:d02605d847f64fd8a67d0da5db68e4ac2021-11-08T10:56:02ZThe urinary excretion of epigenetically modified DNA as a marker of pediatric ALL status and chemotherapy response10.1038/s41598-021-00880-92045-2322https://doaj.org/article/d02605d847f64fd8a67d0da5db68e4ac2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-00880-9https://doaj.org/toc/2045-2322Abstract The active DNA demethylation process may be linked to aberrant methylation and may be involved in leukemogenesis. We investigated the role of epigenetic DNA modifications in childhood acute lymphoblastic leukemia (ALL) diagnostics and therapy monitoring. We analyzed the levels of 5-methyl-2′-deoxycytidine (5-mdC) oxidation products in the cellular DNA and urine of children with ALL (at diagnosis and during chemotherapy, n = 55) using two-dimensional ultra-performance liquid chromatography with tandem mass spectrometry (2D UPLC–MS/MS). Moreover, the expression of Ten Eleven Translocation enzymes (TETs) at the mRNA and protein levels was determined. Additionally, the ascorbate level in the blood plasma was analyzed. Before treatment, the ALL patients had profoundly higher levels of the analyzed modified DNA in their urine than the controls. After chemotherapy, we observed a statistically significant decrease in active demethylation products in urine, with a final level similar to the level characteristic of healthy children. The level of 5-hmdC in the DNA of the leukocytes in blood of the patient group was significantly lower than that of the control group. Our data suggest that urinary excretion of epigenetic DNA modification may be a marker of pediatric ALL status and a reliable marker of chemotherapy response.Rafal RozalskiDaniel GackowskiAleksandra Skalska-BugalaMarta StarczakAgnieszka Siomek-GoreckaEwelina ZarakowskaMartyna ModrzejewskaTomasz DziamanAnna SzpilaKinga LinowieckaJolanta GuzJustyna SzpotanMaciej GawronskiAnna LabejszoLidia GackowskaMarek FoksinskiElwira OlinskaAleksandra WasilowAndrzej KoltanJan StyczynskiRyszard OlinskiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Rafal Rozalski
Daniel Gackowski
Aleksandra Skalska-Bugala
Marta Starczak
Agnieszka Siomek-Gorecka
Ewelina Zarakowska
Martyna Modrzejewska
Tomasz Dziaman
Anna Szpila
Kinga Linowiecka
Jolanta Guz
Justyna Szpotan
Maciej Gawronski
Anna Labejszo
Lidia Gackowska
Marek Foksinski
Elwira Olinska
Aleksandra Wasilow
Andrzej Koltan
Jan Styczynski
Ryszard Olinski
The urinary excretion of epigenetically modified DNA as a marker of pediatric ALL status and chemotherapy response
description Abstract The active DNA demethylation process may be linked to aberrant methylation and may be involved in leukemogenesis. We investigated the role of epigenetic DNA modifications in childhood acute lymphoblastic leukemia (ALL) diagnostics and therapy monitoring. We analyzed the levels of 5-methyl-2′-deoxycytidine (5-mdC) oxidation products in the cellular DNA and urine of children with ALL (at diagnosis and during chemotherapy, n = 55) using two-dimensional ultra-performance liquid chromatography with tandem mass spectrometry (2D UPLC–MS/MS). Moreover, the expression of Ten Eleven Translocation enzymes (TETs) at the mRNA and protein levels was determined. Additionally, the ascorbate level in the blood plasma was analyzed. Before treatment, the ALL patients had profoundly higher levels of the analyzed modified DNA in their urine than the controls. After chemotherapy, we observed a statistically significant decrease in active demethylation products in urine, with a final level similar to the level characteristic of healthy children. The level of 5-hmdC in the DNA of the leukocytes in blood of the patient group was significantly lower than that of the control group. Our data suggest that urinary excretion of epigenetic DNA modification may be a marker of pediatric ALL status and a reliable marker of chemotherapy response.
format article
author Rafal Rozalski
Daniel Gackowski
Aleksandra Skalska-Bugala
Marta Starczak
Agnieszka Siomek-Gorecka
Ewelina Zarakowska
Martyna Modrzejewska
Tomasz Dziaman
Anna Szpila
Kinga Linowiecka
Jolanta Guz
Justyna Szpotan
Maciej Gawronski
Anna Labejszo
Lidia Gackowska
Marek Foksinski
Elwira Olinska
Aleksandra Wasilow
Andrzej Koltan
Jan Styczynski
Ryszard Olinski
author_facet Rafal Rozalski
Daniel Gackowski
Aleksandra Skalska-Bugala
Marta Starczak
Agnieszka Siomek-Gorecka
Ewelina Zarakowska
Martyna Modrzejewska
Tomasz Dziaman
Anna Szpila
Kinga Linowiecka
Jolanta Guz
Justyna Szpotan
Maciej Gawronski
Anna Labejszo
Lidia Gackowska
Marek Foksinski
Elwira Olinska
Aleksandra Wasilow
Andrzej Koltan
Jan Styczynski
Ryszard Olinski
author_sort Rafal Rozalski
title The urinary excretion of epigenetically modified DNA as a marker of pediatric ALL status and chemotherapy response
title_short The urinary excretion of epigenetically modified DNA as a marker of pediatric ALL status and chemotherapy response
title_full The urinary excretion of epigenetically modified DNA as a marker of pediatric ALL status and chemotherapy response
title_fullStr The urinary excretion of epigenetically modified DNA as a marker of pediatric ALL status and chemotherapy response
title_full_unstemmed The urinary excretion of epigenetically modified DNA as a marker of pediatric ALL status and chemotherapy response
title_sort urinary excretion of epigenetically modified dna as a marker of pediatric all status and chemotherapy response
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/d02605d847f64fd8a67d0da5db68e4ac
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