Glutathione S-transferase genotypes in children who develop treatment-related acute myeloid malignancies
Glutathione S-transferase genotypes in children who develop treatment-related acute myeloid malignancies
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DOI：
10.1038/sj.leu.2401660
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发表时间：
2000-02-01
期刊：
影响因子：
11.4
通讯作者：
Relling, MV
中科院分区：
文献类型：
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作者：
Woo, MH;Shuster, JJ;Relling, MV
表鬼臼毒素相关的继发性粒细胞白血病是急性淋巴细胞白血病 (ALL) 治疗的一种破坏性并发症。与治疗相关的粒细胞白血病的危险因素仍未完全确定。谷胱甘肽 S-转移酶 (GST) 活性的遗传缺陷与多种人类恶性肿瘤的高发病率有关。我们的目的是确定 GSTM1、GSTT1 或两者的无效基因型在患有治疗相关骨髓恶性肿瘤的 ALL 儿童中是否比未患治疗相关的儿童更常见。采用 PCR 技术对 302 名 ALL 儿童的 GSTM1 和 GSTT1 无效基因型进行了检测，其中 57 名儿童随后还出现了与治疗相关的急性髓系白血病或骨髓增生异常综合征。在未发生治疗相关骨髓恶性肿瘤的 ALL 儿童中，GSTM1 和 GSTT1 野生型、GSTM1 缺失-GSTT1 野生型、GSTM1 野生型-GSTT1 缺失以及 GSTM1 和 GSTT1 缺失基因型的频率分别为 40%、42%、9% 和 9%。患急性髓系恶性肿瘤的患者的相应频率分别为 42%、32%、11% 和 16%（P = 0.26）。与男性 ALL 对照患者相比，在发生骨髓恶性肿瘤的男性患者中观察到 GST 无效基因型频率有统计学意义的显着增加 (P = 0.036)，但在女性患者中未观察到 (P = 0.51)。此外，在控制性别和种族的情况下，对骨髓恶性肿瘤的可能预测因子进行逻辑回归分析，未发现 GSTM1 或 GSTT1 无效基因型（分别为 P = 0.62 和 0.11）与治疗相关恶性肿瘤之间的关联。我们的数据表明，GSTM1 和 GSTT1 无效基因型可能不会诱发表鬼臼毒素相关的骨髓恶性肿瘤。
Epipodophyllotoxin-associated secondary myeloid leukemia is a devastating complication of acute lymphoblastic leukemia (ALL) therapy. The risk factors for treatment-related myeloid leukemia remain incompletely defined. Genetic deficiencies in glutathione S-transferase (GST) activities have been linked to higher frequencies of a number of human malignancies. Our objective was to determine whether the null genotype for GSTM1, GSTT1, or both, was more frequent in children with ALL who developed treatment-related myeloid malignancies as compared to those who did not. A PCR technique was used to assay for the null genotype for GSTM1 and GSTT1 in 302 children with ALL, 57 of whom also subsequently developed treatment-related acute myeloid leukemia or myelodysplastic syndrome. Among children with ALL who did not develop treatment-related myeloid malignancies, the frequencies of GSTM1 and GSTT1 wild-type, GSTM1 null-GSTT1 wild-type, GSTM1 wild-type-GSTT1 null, and GSTM1 and GSTT1 null genotypes were 40%, 42%, 9% and 9%, respectively. The corresponding frequencies for patients who developed acute myeloid malignancies were 42%, 32%, 11% and 16%, respectively (P = 0.26). A statistically significant increase in the frequency of the GST null genotype was observed in male patients who developed myeloid malignancies as compared to male ALL control patients (P = 0.036), but was not observed in female patients (P = 0.51). Moreover, a logistic regression analysis of possible predictors for myeloid malignancies, controlling for gender and race, did not reveal an association of GSTM1 or GSTT1 null genotypes (P = 0.62 and 0.11, respectively) with treatment-related malignancies. Our data suggest that GSTM1 and GSTT1 null genotypes may not predispose to epipodophyllotoxin-associated myeloid malignancies.