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

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 extracted from peripheral blood Mononuclear cells (MNCs) using the Trizol method. Then cDNAs were synthesized. Gene expression was quantified with Real-Time PCR System. 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's group. Intra-group comparisons also revealed increased expression of ABCG2 in Accelerated Phase (AP)-Blastic Crisis (BC) patients compared to Chronic Phase (CP) patients. Whereas, increased expression of MRP1 in AP-BC patients was not statistically significant. Conclusion: Considering the wide spectrum of (ATP Binding Cassette) ABC transporter superfamily substrates, they can play an important 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 the cells from the therapeutic effects of medications. On the other hand, these transporters are able to 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.

Keywords

• ABCG2
• MRP1
• CML
• Imatinib
• Gene expression