Rahgozar Soheila, Moafi Alireza, Abedi Marjan, Entezar-E-Ghaem Mansureh, Moshtaghian Jamal, Ghaedi Kamran, Esmaeili Abolghasem, Montazeri Fatemeh
Division of Cell and Molecular Biology; Department of Biology; Faculty of Science; University of Isfahan; Isfahan, Iran.
Department of Paediatric-Oncology; Sayed ol Shohada Hospital; Isfahan University of Medical Sciences; Isfahan, Iran.
Cancer Biol Ther. 2014 Jan;15(1):35-41. doi: 10.4161/cbt.26603. Epub 2013 Oct 21.
Multidrug resistance (MDR) is an important cause of treatment failure in acute lymphoblastic leukemia (ALL). The ABC family of membrane transporters is proposed, albeit with controversy, to be involved in this process. The present study aims to investigate the mRNA expression profile of several genes of this family, including ABCA2, ABCA3, ABCB1/MDR1, MRP1/ABCC1, MRP3/ABCC3, ABCG2/BCRP, and the intracellular transporter MVP/LRP, in childhood ALL, and to evaluate their association with response to therapy. Some genes in the present research are being studied for the first time in Iran. Using quantitative real-time PCR, we evaluated 27 children with ALL at diagnosis and 15 children with normal bone marrow. The status of response to therapy was assessed one year after the onset of therapy through investigating the IgH/TCRγ gene rearrangements. Our findings indicate a considerable and direct relationship between mRNA expression levels of ABCA2, ABCA3, MDR1, and MRP1 genes and positive minimal residual disease (MRD) measured after one year of treatment. Statistical analysis revealed that expression of these genes higher than the cutoff point will raise the risk of MRD by 15-, 6.25-, 12-, and 9-fold, respectively. No relationship was found between of MVP/LRP, MRP3 and ABCG2 genes expression and ALL prognoses. Considering the direct and significant relationship between the increased expression of ABCA2, ABCA3, MDR1, and MRP1 genes and positive risk of MRD in children with ALL, evaluating the expression profile of these genes on diagnosis may identify high risk individuals and help plan a more efficient treatment strategy.
多药耐药（MDR）是急性淋巴细胞白血病（ALL）治疗失败的重要原因。膜转运蛋白ABC家族虽存在争议，但被认为参与了这一过程。本研究旨在调查该家族几个基因的mRNA表达谱，包括ABCA2、ABCA3、ABCB1/MDR1、MRP1/ABCC1、MRP3/ABCC3、ABCG2/BCRP以及细胞内转运蛋白MVP/LRP，在儿童ALL中的表达情况，并评估它们与治疗反应的相关性。本研究中的一些基因在伊朗尚属首次研究。我们采用定量实时PCR技术，对27例ALL诊断患儿和15例正常骨髓患儿进行了评估。通过检测IgH/TCRγ基因重排，在治疗开始一年后评估治疗反应状态。我们的研究结果表明，ABCA2、ABCA3、MDR1和MRP1基因的mRNA表达水平与治疗一年后检测到的阳性微小残留病（MRD）之间存在显著的直接关系。统计分析显示，这些基因的表达高于临界值将分别使MRD风险提高15倍、6.25倍、12倍和9倍。未发现MVP/LRP、MRP3和ABCG2基因表达与ALL预后之间存在关联。鉴于ABCA2、ABCA3、MDR1和MRP1基因表达增加与ALL患儿MRD阳性风险之间存在直接且显著的关系，在诊断时评估这些基因的表达谱可能有助于识别高危个体，并有助于制定更有效的治疗策略。
