Global methylation in relation to methotrexate-induced oral mucositis in children with acute lymphoblastic leukemia.
<h4>Background</h4>Children with acute lymphoblastic leukemia (ALL) often suffer from toxicity of chemotherapeutic drugs such as Methotrexate (MTX). Previously, we reported that 20% of patients receiving high-dose MTX developed oral mucositis. MTX inhibits folate metabolism, which is ess...
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| Language: | English |
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Public Library of Science (PLoS)
2018-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0199574&type=printable |
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| author | Natanja Oosterom Pieter H Griffioen Marissa A H den Hoed Rob Pieters Robert de Jonge Wim J E Tissing Marry M van den Heuvel-Eibrink Sandra G Heil |
| author_facet | Natanja Oosterom Pieter H Griffioen Marissa A H den Hoed Rob Pieters Robert de Jonge Wim J E Tissing Marry M van den Heuvel-Eibrink Sandra G Heil |
| author_sort | Natanja Oosterom |
| collection | DOAJ |
| description | <h4>Background</h4>Children with acute lymphoblastic leukemia (ALL) often suffer from toxicity of chemotherapeutic drugs such as Methotrexate (MTX). Previously, we reported that 20% of patients receiving high-dose MTX developed oral mucositis. MTX inhibits folate metabolism, which is essential for DNA methylation. We hypothesize that MTX inhibits DNA methylation, which results into adverse effects. We studied DNA methylation markers during high-dose methotrexate treatment in pediatric acute lymphoblastic leukemia (ALL) in relation to developing oral mucositis.<h4>Materials & methods</h4>S-Adenosyl-Methionine (SAM) and S-Adenosyl-Homocysteine (SAH) levels and LINE1 DNA methylation were measured prospectively before and after high-dose methotrexate (HD-MTX 4 x 5g/m2) therapy in 82 children with ALL. Methotrexate-induced oral mucositis was registered prospectively. Oral mucositis (grade ≥ 3 National Cancer Institute Criteria) was used as clinical endpoint.<h4>Results</h4>SAM levels decreased significantly during methotrexate therapy (-16.1 nmol/L (-144.0 -+46.0), p<0.001), while SAH levels and the SAM:SAH ratio did not change significantly. LINE1 DNA methylation (+1.4% (-1.1 -+6.5), p<0.001) increased during therapy. SAM and SAH levels were not correlated to LINE1 DNA methylation status. No association was found between DNA methylation markers and developing oral mucositis.<h4>Conclusions</h4>This was the first study that assessed DNA methylation in relation to MTX-induced oral mucositis in children with ALL. Although global methylation markers did change during methotrexate therapy, methylation status was not associated with developing oral mucositis. |
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| id | doaj.art-436c64c86ccf458d979c75358d09a3c1 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2025-03-14T13:36:02Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
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| spelling | doaj.art-436c64c86ccf458d979c75358d09a3c12025-02-28T05:32:49ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01137e019957410.1371/journal.pone.0199574Global methylation in relation to methotrexate-induced oral mucositis in children with acute lymphoblastic leukemia.Natanja OosteromPieter H GriffioenMarissa A H den HoedRob PietersRobert de JongeWim J E TissingMarry M van den Heuvel-EibrinkSandra G Heil<h4>Background</h4>Children with acute lymphoblastic leukemia (ALL) often suffer from toxicity of chemotherapeutic drugs such as Methotrexate (MTX). Previously, we reported that 20% of patients receiving high-dose MTX developed oral mucositis. MTX inhibits folate metabolism, which is essential for DNA methylation. We hypothesize that MTX inhibits DNA methylation, which results into adverse effects. We studied DNA methylation markers during high-dose methotrexate treatment in pediatric acute lymphoblastic leukemia (ALL) in relation to developing oral mucositis.<h4>Materials & methods</h4>S-Adenosyl-Methionine (SAM) and S-Adenosyl-Homocysteine (SAH) levels and LINE1 DNA methylation were measured prospectively before and after high-dose methotrexate (HD-MTX 4 x 5g/m2) therapy in 82 children with ALL. Methotrexate-induced oral mucositis was registered prospectively. Oral mucositis (grade ≥ 3 National Cancer Institute Criteria) was used as clinical endpoint.<h4>Results</h4>SAM levels decreased significantly during methotrexate therapy (-16.1 nmol/L (-144.0 -+46.0), p<0.001), while SAH levels and the SAM:SAH ratio did not change significantly. LINE1 DNA methylation (+1.4% (-1.1 -+6.5), p<0.001) increased during therapy. SAM and SAH levels were not correlated to LINE1 DNA methylation status. No association was found between DNA methylation markers and developing oral mucositis.<h4>Conclusions</h4>This was the first study that assessed DNA methylation in relation to MTX-induced oral mucositis in children with ALL. Although global methylation markers did change during methotrexate therapy, methylation status was not associated with developing oral mucositis.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0199574&type=printable |
| spellingShingle | Natanja Oosterom Pieter H Griffioen Marissa A H den Hoed Rob Pieters Robert de Jonge Wim J E Tissing Marry M van den Heuvel-Eibrink Sandra G Heil Global methylation in relation to methotrexate-induced oral mucositis in children with acute lymphoblastic leukemia. PLoS ONE |
| title | Global methylation in relation to methotrexate-induced oral mucositis in children with acute lymphoblastic leukemia. |
| title_full | Global methylation in relation to methotrexate-induced oral mucositis in children with acute lymphoblastic leukemia. |
| title_fullStr | Global methylation in relation to methotrexate-induced oral mucositis in children with acute lymphoblastic leukemia. |
| title_full_unstemmed | Global methylation in relation to methotrexate-induced oral mucositis in children with acute lymphoblastic leukemia. |
| title_short | Global methylation in relation to methotrexate-induced oral mucositis in children with acute lymphoblastic leukemia. |
| title_sort | global methylation in relation to methotrexate induced oral mucositis in children with acute lymphoblastic leukemia |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0199574&type=printable |
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