Nadimi Motahareh, Rahgozar Soheila, Moafi Alireza, Tavassoli Manoochehr, Mesrian Tanha Hamzeh
Division of Cell and Molecular Biology, Department of Biology, Faculty of Science, University of Isfahan, Isfahan, Iran.
Division of Cell and Molecular Biology, Department of Biology, Faculty of Science, University of Isfahan, Isfahan, Iran.
Cancer Genet. 2016 Jul-Aug;209(7-8):348-53. doi: 10.1016/j.cancergen.2016.06.005. Epub 2016 Jun 16.
Acute leukemia is the most common cancer in children and involves several factors that contribute to the development of multidrug resistance and treatment failure. According to our recent studies, the BAALC gene is identified to have high mRNA expression levels in childhood acute lymphoblastic leukemia (ALL) and those with multidrug resistance. Several polymorphisms are associated with the expression of this gene. To date, there has been no study on the rs62527607 [GT] single nucleotide polymorphism (SNP) of BAALC gene and its link with childhood acute lymphoblastic and myeloid leukemia (AML). The purpose of this study is to evaluate the prevalence of this polymorphism in pediatric acute leukemia, as well as its relationship with prognosis. DNA samples were extracted from bone marrow slides of 129 children with ALL and 16 children with AML. The rs62527607 [GT] SNP was evaluated using mismatch polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)-based analysis. The association between the SNP alleles and patient disease-free survival was then assessed. The prevalence of the T-allele of rs62527607 [GT] SNP in childhood T-ALL and pre-B-ALL was 28.3% and 11.2%, respectively. In the pre-B-ALL patients, 3 year disease free survival was associated with the GG genotype. Results showed a robust association between the rs62527607 SNP and the risk of relapse in ALL, but not AML, patients. T-ALL patients with the GT genotype had an 8.75 fold higher risk of relapse. The current study demonstrates a significant association between the genotype GT and the polymorphic allele G424T, and introduces this SNP as a negative prognostic factor in children with ALL.
急性白血病是儿童中最常见的癌症,涉及多种导致多药耐药和治疗失败的因素。根据我们最近的研究,发现BAALC基因在儿童急性淋巴细胞白血病(ALL)和多药耐药患者中具有较高的mRNA表达水平。该基因的表达与几种多态性有关。迄今为止,尚未有关于BAALC基因的rs62527607 [GT]单核苷酸多态性(SNP)及其与儿童急性淋巴细胞白血病和髓系白血病(AML)关系的研究。本研究的目的是评估这种多态性在小儿急性白血病中的患病率及其与预后的关系。从129例ALL患儿和16例AML患儿的骨髓涂片提取DNA样本。使用基于错配聚合酶链反应-限制性片段长度多态性(PCR-RFLP)的分析方法评估rs62527607 [GT] SNP。然后评估SNP等位基因与患者无病生存率之间的关联。rs62527607 [GT] SNP的T等位基因在儿童T-ALL和前B-ALL中的患病率分别为28.3%和11.2%。在前B-ALL患者中,3年无病生存率与GG基因型相关。结果显示,rs62527607 SNP与ALL患者(而非AML患者)的复发风险之间存在密切关联。GT基因型的T-ALL患者复发风险高8.75倍。本研究表明基因型GT与多态性等位基因G424T之间存在显著关联,并将该SNP作为ALL患儿的不良预后因素。