甲氨蝶呤相关基因多态性在儿童急性淋巴细胞白血病大剂量甲氨蝶呤治疗的影响

Impact of Methotrexate-Related Genetic Polymorphisms in High-Dose Methotrexate Therapy for Childhood Acute Lymphoblastic Leukaemia

急性淋巴细胞白血病(Acute Lymphoblastic Luekemia, ALL)是儿童发病率最高的恶性肿瘤,经过化疗等治疗后ALL儿童的预后大大改善,但复发仍是现在一大难题。大剂量甲氨蝶呤(high-dose metho-trexate, HDMTX)有效地降低了ALL中枢神经系统的复发。但实际临床中HDMTX治疗后不同个体的疗效和药物不良反应(adverse drugreaction, ADR)表现有差异,基因组所具有的基因多态性与MTX化疗的ADR之间有重要关联。本综述旨在总结国内外所研究的一些相关基因位点多态性与MTX化疗的ADR的关联性。例如:亚甲基四氢叶酸还原酶(methotrexate reductase, MTHFR)基因、多耐药蛋白(ATP-binding cassette subfamily B member 1, ABCB1)基因、丝氨酸羟甲基四氢叶酸还原酶1 serine hydroxymethyl transferase 1, SHMT1)基因、有机阴离子转运体(solute carrier organic anion trans-porter 1B1, SLCO1B1)基因。

Acute lymphoblastic leukaemia is the most prevalent malignancy in children. The prognosis for children with ALL has improved considerably after treatment with chemotherapy and other thera-pies, but relapse is still a major challenge today. High-dose methotrexate has been effective in re-ducing relapse in the central nervous system of ALL. However, in actual clinical practice, there are differences in the efficacy and manifestation of adverse drug reactions in different individuals after HDMTX treatment, and there is an important association between genetic polymorphisms and ADR of MTX chemotherapy. The aim of this review is to summarize the association between polymor-phisms at some relevant genetic loci and the ADR of MTX chemotherapy. For example: methylene-tetrahydrofolate reductase gene, multidrugresistance protein gene, serine hydroxymethyltetrahy-drofolate reductase gene and organic anion transporter gene.