TP53 codon 72 polymorphism predicts chronic myeloid leukemia susceptibility and treatment outcome
TP53 codon 72 polymorphism predicts chronic myeloid leukemia susceptibility and treatment outcome
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DOI：
10.1016/j.bcmd.2016.05.007
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发表时间：
2016-07-01
影响因子：
2.3
通讯作者：
Fundia, Ariela
中科院分区：
文献类型：
--
作者：
Weich, Natalia;Ferri, Cristian;Fundia, Ariela
BCR-ABL1基因是慢性粒细胞白血病（CML）的关键分子标志物，但目前尚不清楚哪些分子因素可能影响CML风险或导致对酪氨酸激酶抑制剂（TKI）的不同反应。本研究的目的是探讨 TP53 c.213 G > C(Arg72Pro; rs1042522) 多态性对 CML 风险的影响及其与临床结果的相关性。通过 PCR-RFLP 对 141 名接受治疗的 CML 患者和 141 名性别和年龄匹配的健康个体的外周血样本进行了基因分型。通过逻辑回归分析评估疾病外显率的标准遗传模型，并采用 Kaplan-Meier 方法估计生存曲线。我们的研究表明，考虑到隐性模型，TP53 c.213 G > C 多态性可能与 CML 的发展有关（p=0.01；OR：0.19；CI：0.06-0.68）。此外，在男性和 50 岁以下的患者中发现这种多态性分布不均匀（p = 0.02）。根据临床反应，TP53-GG 基因型与较高水平的 BCR-ABL1 转录物 (p = 0.04) 和较短的无事件生存期 (p = 0.04) 相关。此外，发现无失败生存期（p=0.06）和伊马替尼失败时间（p=0.08）具有显着性趋势。总之，我们的数据表明： TP53 c.213 G > C 可能是 CML 易感性和临床结果的潜在生物标志物。 (C) 2016 Elsevier Inc. 保留所有权利。
BCR-ABL1 gene is a key molecular marker of chronic myeloid leukemia (CML), but it is still unclear which molecular factors may influence CML risk or lead to variable responses to tyrosine kinase inhibitors (TKIs). The aim of this study was to investigate the impact of TP53 c.213 G > C(Arg72Pro; rs1042522) polymorphism on CML risk and its correlation with clinical outcome. Peripheral blood samples from 141 treated CML patients and 141 sex-and age-matched healthy individuals were genotyped by PCR-RFLP. Standard genetic models for disease penetrance were evaluated by logistic regression analysis and Kaplan-Meier method was performed to estimate survival curves. Our study suggests that TP53 c.213 G > C polymorphism may be involved in CML development considering a recessive model (p=0.01; OR: 0.19; CI: 0.06-0.68). In addition, a non-homogenous distribution was found for this polymorphism in males and patients youngers than 50 years (p = 0.02). According to clinical response, TP53-GG genotype was associated with higher levels of BCR-ABL1 transcripts (p = 0.04) and shorter event free survival (p= 0.04). Moreover, a trend toward significance was found for failure free survival (p= 0.06) and time to imatinib failure (p= 0.08). In conclusion, our data suggest that a; TP53 c.213 G > C may be a potential biomarker of CML susceptibility and clinical outcome. (C) 2016 Elsevier Inc. All rights reserved.