MTX-induced white matter changes are associated with polymorphisms of methionine metabolism.
Methotrexate (MTX) is a folate antagonist inhibiting nucleic acid and methionine synthesis. Methionine is necessary for CNS myelination. In 42 patients with primary CNS lymphoma (PCNSL) treated with a systemic and intraventricular high-dose MTX-based polychemotherapy, the presence of a risk haplotype defined by polymorphisms influencing methionine metabolism referred a relative risk for CNS white matter changes of 4.7 (p = 0.001). The authors conclude that methionine metabolism influences MTX neurotoxicity.
Linnebank
M
M
Department of Neurology, University Hospital Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany. Michael.Linnebank@ukb.uni-bonn.de
Pels
H
H
Kleczar
N
N
Farmand
S
S
Fliessbach
K
K
Urbach
H
H
Orlopp
K
K
Klockgether
T
T
Schmidt-Wolf
I G H
IG
Schlegel
U
U
D000368:Aged; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016543:Central Nervous System Neoplasms / Q000188:drug therapy*; D004252:DNA Mutational Analysis; D003711:Demyelinating Diseases / Q000139:chemically induced* / Q000235:genetics / Q000503:physiopathology; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D005492:Folic Acid / Q000378:metabolism; D005493:Folic Acid Antagonists / Q000008:administration & dosage / Q000009:adverse effects; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D006239:Haplotypes; D006801:Humans; D008223:Lymphoma / Q000188:drug therapy*; D008297:Male; D008715:Methionine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects*; D008875:Middle Aged; D009186:Myelin Sheath / Q000187:drug effects / Q000378:metabolism; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009498:Neurotoxins / Q000008:administration & dosage / Q000009:adverse effects; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors; D012436:S-Adenosylmethionine / Q000378:metabolism
D005493:Folic Acid Antagonists; D009498:Neurotoxins; D012436:S-Adenosylmethionine; D005492:Folic Acid; D008715:Methionine; D008727:Methotrexate