Organista-Nava Jorge, Gómez-Gómez Yazmín, Illades-Aguiar Berenice, Rivera-Ramírez Ana Bertha, Saavedra-Herrera Mónica Virginia, Leyva-Vázquez Marco Antonio
Laboratory of Molecular Biomedicine, School of Chemical-Biological Sciences, Guerrero State University, Chilpancingo, Guerrero 39090, Mexico.
Research Department, State Cancer Institute, Arturo Beltran Ortega, Acapulco, Guerrero 39570, Mexico.
Oncol Lett. 2018 Jun;15(6):8405-8411. doi: 10.3892/ol.2018.8429. Epub 2018 Apr 4.
Dihydrofolate reductase (DHFR) has an important function in DNA synthesis and is a target of methotrexate, which is a crucial treatment option for acute lymphoblastic leukemia (ALL). However, the number of studies conducted to date on DHFR expression in childhood ALL is limited. The aim of the present study was to determine whether the expression of DHFR is associated with survival in childhood ALL. The expression of DHFR in 96 children with ALL and 100 control individuals was determined using reverse transcription-quantitative polymerase chain reaction. The results of the present study demonstrated that the expression of DHFR mRNA in children with ALL was significantly increased (P<0.001), compared with that in the control group. In addition, increased levels of DHFR mRNA were observed in patients with B-cell lineage, compared with patients with T-cell lineage ALL (P<0.05). The Kaplan-Meier estimator analysis revealed that children with ALL who exhibited increased levels of DHFR mRNA had a decreased overall survival time (P<0.05). It was observed that certain patient prognostic features (including age, sex, white blood cell count and high DHFR expression), are associated with poor survival (log-rank test, P<0.05). Therefore, the results of the present study indicated that DHFR upregulation is a factor for poor survival in ALL.
二氢叶酸还原酶(DHFR)在DNA合成中具有重要作用,是甲氨蝶呤的作用靶点,甲氨蝶呤是急性淋巴细胞白血病(ALL)的关键治疗选择。然而,迄今为止关于儿童ALL中DHFR表达的研究数量有限。本研究的目的是确定DHFR的表达是否与儿童ALL的生存率相关。使用逆转录定量聚合酶链反应测定了96例ALL患儿和100例对照个体中DHFR的表达。本研究结果表明,与对照组相比,ALL患儿中DHFR mRNA的表达显著增加(P<0.001)。此外,与T细胞系ALL患者相比,B细胞系患者中观察到DHFR mRNA水平升高(P<0.05)。Kaplan-Meier估计分析显示,DHFR mRNA水平升高的ALL患儿总生存时间缩短(P<0.05)。观察到某些患者预后特征(包括年龄、性别、白细胞计数和高DHFR表达)与生存不良相关(对数秩检验,P<0.05)。因此,本研究结果表明DHFR上调是ALL患者生存不良的一个因素。