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

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<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 with developing oral mucositis.
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.