Global methylation in relation to methotrexate-induced oral mucositis in children with acute lymphoblastic leukemia

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

doi:10.1371/journal.pone.0199574

Global methylation in relation to methotrexate-induced oral mucositis in children with acute lymphoblastic leukemia

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

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Abstract

Background

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.

Materials & methods

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.

Results

SAM levels decreased significantly during methotrexate therapy (-16.1 nmol/L (-144.0 - +46.0), p

Conclusions

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.

Original language	English
Article number	0199574
Number of pages	10
Journal	PLoS ONE
Volume	13
Issue number	7
DOIs	https://doi.org/10.1371/journal.pone.0199574
Publication status	Published - 9-Jul-2018

Keywords

DNA METHYLATION
S-ADENOSYLHOMOCYSTEINE
ONCOLOGY GROUP
HYPOMETHYLATION
ADENOSYLMETHIONINE
METHIONINE
EXPRESSION
ARTHRITIS
TOXICITY
SURVIVAL

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Data from: Global methylation in relation to methotrexate-induced oral mucositis in children with acute lymphoblastic leukemia
Oosterom, N. (Creator), Griffioen, P. H. (Creator), den Hoed, M. A. H. (Creator), Pieters, R. (Creator), de Jonge, R. (Creator), Tissing, W. (Creator), van den Heuvel-Eibrink, M. M. (Creator) & Heil, S. G. (Creator), University of Groningen, 17-Jul-2018
DOI: 10.5061/dryad.t3g1vc3
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@article{e334db127ec94c75ab56e385639239fe,

title = "Global methylation in relation to methotrexate-induced oral mucositis in children with acute lymphoblastic leukemia",

abstract = "BackgroundChildren 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.Materials & methodsS-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.ResultsSAM levels decreased significantly during methotrexate therapy (-16.1 nmol/L (-144.0 - +46.0), pConclusionsThis 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.",

keywords = "DNA METHYLATION, S-ADENOSYLHOMOCYSTEINE, ONCOLOGY GROUP, HYPOMETHYLATION, ADENOSYLMETHIONINE, METHIONINE, EXPRESSION, ARTHRITIS, TOXICITY, SURVIVAL",

author = "Natanja Oosterom and Griffioen, {Pieter H.} and {den Hoed}, {Marissa A. H.} and Rob Pieters and {de Jonge}, Robert and Tissing, {Wim J. E.} and {van den Heuvel-Eibrink}, {Marry M.} and Heil, {Sandra G.}",

year = "2018",

month = jul,

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doi = "10.1371/journal.pone.0199574",

language = "English",

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T1 - Global methylation in relation to methotrexate-induced oral mucositis in children with acute lymphoblastic leukemia

AU - Oosterom, Natanja

AU - Griffioen, Pieter H.

AU - den Hoed, Marissa A. H.

AU - Pieters, Rob

AU - de Jonge, Robert

AU - Tissing, Wim J. E.

AU - van den Heuvel-Eibrink, Marry M.

AU - Heil, Sandra G.

PY - 2018/7/9

Y1 - 2018/7/9

N2 - BackgroundChildren 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.Materials & methodsS-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.ResultsSAM levels decreased significantly during methotrexate therapy (-16.1 nmol/L (-144.0 - +46.0), pConclusionsThis 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.

AB - BackgroundChildren 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.Materials & methodsS-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.ResultsSAM levels decreased significantly during methotrexate therapy (-16.1 nmol/L (-144.0 - +46.0), pConclusionsThis 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.

KW - DNA METHYLATION

KW - S-ADENOSYLHOMOCYSTEINE

KW - ONCOLOGY GROUP

KW - HYPOMETHYLATION

KW - ADENOSYLMETHIONINE

KW - METHIONINE

KW - EXPRESSION

KW - ARTHRITIS

KW - TOXICITY

KW - SURVIVAL

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DO - 10.1371/journal.pone.0199574

M3 - Article

SN - 1932-6203

VL - 13

JO - PLoS ONE

JF - PLoS ONE

IS - 7

M1 - 0199574

ER -

Global methylation in relation to methotrexate-induced oral mucositis in children with acute lymphoblastic leukemia

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Data from: Global methylation in relation to methotrexate-induced oral mucositis in children with acute lymphoblastic leukemia

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