Pharmacogenetic studies in children with acute lymphoblastic leukemia in Argentina
Pharmacogenetic studies in children with acute lymphoblastic leukemia in Argentina
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阿根廷儿童急性淋巴细胞白血病的药物遗传学研究
DOI：
10.3109/10428194.2014.951844
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发表时间：
2015
影响因子：
2.6
通讯作者：
M. Felice
中科院分区：
文献类型：
--
作者：
H. Aráoz;Karina D'Aloi;M. Foncuberta;Christian Germán Sanchez La Rosa;C. Alonso;L. Chertkoff;M. Felice
摘要本研究的目的是评估最常见的遗传变异亚甲基四氢叶酸还原酶（MTHFR），巯基嘌呤甲基转移酶（TPMT）和谷胱甘肽-S-转移酶（GST）对阿根廷儿童急性淋巴细胞白血病（ALL）治疗结果的影响。分析了286例接受两种基于柏林-法兰克福-明斯特（BFM）方案治疗的ALL患者。研究了10种遗传变异。在巩固阶段评价毒性。接受2 g/m2/d甲氨蝶呤治疗且MTHFR中至少携带一个677 T等位基因的儿童发生严重白细胞减少症（p = 0.004）和中性粒细胞减少症（p = 0.003）的风险增加。具有杂合TPMT基因型的中危（IR）患者比具有野生型基因型的患者有更高的无事件生存概率。MTHFR多态性的基因分型可能有助于优化巩固治疗，减少相关的严重血液学毒性。进一步的研究是必要的，以建立有用的MTHFR和TPMT变异作为额外的标志物，以预测IR组的结果。
Abstract The aim of this study was to evaluate the influence of the most common genetic variants in methylenetetrahydrofolate reductase (MTHFR), thiopurine methyltransferase (TPMT) and glutathione-S-transferases (GSTs) on the outcome of acute lymphoblastic leukemia (ALL) treatment in Argentinean children. Two hundred and eighty-six patients with ALL treated with two Berlin–Frankfurt–Münster (BFM)-based protocols were analyzed. Ten genetic variants were studied. Toxicity was evaluated during the consolidation phase. Children who received 2 g/m2/day of methotrexate and carried at least one 677T allele in MTHFR showed an increased risk of developing severe leukopenia (p = 0.004) and neutropenia (p = 0.003). Intermediate-risk (IR) patients with a heterozygous TPMT genotype had a higher probability of event-free survival than those with a wild-type genotype. Genotyping of MTHFR polymorphisms might be useful to optimize consolidation therapy, reducing the associated severe hematologic toxicity. Further studies are necessary to establish the usefulness of MTHFR and TPMT variants as additional markers to predict outcome in the IR group.
影响因子：
45.3
作者：
Evans, WE;Hon, YY;Relling, MV
通讯作者：
Relling, MV
影响因子：
20.3
作者：
Rocha, JCC;Cheng, C;Relling, MV
通讯作者：
Relling, MV
影响因子：
10.3
作者：
Relling, MV;Hancock, ML;Evans, WE
通讯作者：
Evans, WE