Investigation of MRP1 and ABCG2 Gene Expression in Chronic Myeloid Leukemia (CML) Patients

Saeed Solali, Masoumeh Fardi, S. Almasi, M. Aliparasti
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Abstract

Background: This study evaluated and compared the quantitative expression of multidrug resistance-associated protein 1 (MRP1) and ATP-binding cassette subfamily G member 2 (ABCG2), two Multidrug Resistance (MDR) related genes, in 30 CML patients and 27 normal subjects. Methods: Total RNA was isolated from peripheral blood mononuclear cells (MNCs) using the Trizol reagent. Then cDNAs were synthesized. Gene expression was quantified using Real-Time PCR System. The relative expression of target genes was calculated using the 2-ΔΔCt method. Results: High expression of MRP1 and ABCG2 mRNAs were detected in the patient group. Intra-group comparisons also revealed increased expression of ABCG2 in Accelerated Phase (AP)-Blastic Crisis (BC) patients compared to Chronic Phase (CP) patients. At the same time, the increased expression of MRP1 in AP-BC patients was not statistically significant. Conclusion: Considering the broad spectrum of ATP Binding Cassette (ABC) transporter superfamily substrates, they can play an essential role in cell fate determination. High expression of MRP1 and ABCG2 genes can result in the efflux of therapeutic agents and subsequent reduction in their intracellular concentration. This mechanism finally protects cells from the therapeutic effects of medications. On the other hand, these transporters can export growth factors out of the cell. Such exported molecules may have a growth-inducing effect on adjacent cells. These are the possible mechanisms for the participation of MRP1 and ABCG2 genes in conferring drug resistance to CML cells.
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慢性髓性白血病(CML)患者MRP1和ABCG2基因表达的研究
背景:本研究评估并比较了30例CML患者和27例正常人多药耐药(MDR)相关基因MRP1和atp结合盒亚家族G成员2 ABCG2的定量表达。方法:采用Trizol试剂从外周血单个核细胞(MNCs)中分离总RNA。然后合成cdna。采用Real-Time PCR系统定量检测基因表达。用2-ΔΔCt法计算靶基因的相对表达量。结果:患者组MRP1和ABCG2 mrna高表达。组内比较还显示,与慢性期(CP)患者相比,加速期(AP)-母细胞危象(BC)患者中ABCG2的表达增加。同时,MRP1在AP-BC患者中的表达升高无统计学意义。结论:考虑到ATP Binding Cassette (ABC)转运体超家族底物的广谱性,它们可能在决定细胞命运中发挥重要作用。MRP1和ABCG2基因的高表达可导致治疗剂的外排和随后的细胞内浓度降低。这种机制最终保护细胞不受药物治疗效果的影响。另一方面,这些转运蛋白可以将生长因子输出到细胞外。这种输出的分子可能对邻近细胞有诱导生长的作用。这些都是MRP1和ABCG2基因参与CML细胞耐药的可能机制。
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审稿时长
12 weeks
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