Laverdière Caroline, Chiasson Sonia, Costea Irina, Moghrabi Albert, Krajinovic Maja
Centre de Recherche, Hôpital Sainte-Justine, Montréal, QC, Canada.
Blood. 2002 Nov 15;100(10):3832-4. doi: 10.1182/blood.V100.10.3832.
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 G(80)A 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 G(80)A and both MTX plasma levels and childhood ALL outcome. Children with the A(80) variant had worse prognoses than patients with the GG genotype (P =.04), as shown by event-free survival estimates. Patients homozygous for A(80) 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.
甲氨蝶呤（MTX）是用于治疗儿童急性淋巴细胞白血病（ALL）的化疗方案中的关键化合物。对这种药物产生耐药性的原因可能有多种，其中细胞摄取改变可能会妨碍治疗效果。最近，在编码主要MTX转运蛋白的还原型叶酸载体基因（RFC1）中发现了一种G(80)A多态性。在此，我们评估了G(80)A基因多态性与MTX血浆水平及儿童ALL预后之间的关联。无事件生存估计显示，携带A(80)变体的儿童预后比GG基因型患者差（P = 0.04）。A(80)纯合子患者的MTX水平高于其他基因型组（P = 0.004）。文中讨论了观察到的关联的可能解释；然而，需要进行更多实验来了解潜在机制。
