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Blood, 15 November 2002, Vol. 100, No. 10, pp. 3832-3834
BRIEF REPORT
Polymorphism G80A in the reduced folate carrier gene
and its relationship to methotrexate plasma levels and outcome of
childhood acute lymphoblastic leukemia
Caroline Laverdière,
Sonia Chiasson,
Irina Costea,
Albert Moghrabi, and
Maja Krajinovic
From the Centre de Recherche, Hôpital
Sainte-Justine, Montréal, QC, Canada.
Methotrexate (MTX) is a key compound of chemotherapeutic regimens
used in the treatment of childhood acute lymphoblastic leukemia (ALL).
Resistance to this drug may arise by, among other factors, altered
cellular uptake that may hamper the efficacy of the treatment. Recently, a G80A polymorphism has been described in the
reduced folate carrier gene (RFC1), which encodes
the major MTX transporter. Here, we assessed the association between
the genetic polymorphisms G80A and both MTX plasma levels
and childhood ALL outcome. Children with the A80 variant
had worse prognoses than patients with the GG genotype
(P = .04), as shown by event-free survival estimates. Patients homozygous for A80 had higher levels of MTX
(P = .004) than the other genotype groups. Possible
explanations for observed associations are discussed; however,
additional experiments are required to achieve understanding of the
underlying mechanism.
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