Quantitative evaluation of Imatib efflux and influx transporters expression in Chronic Myeloid Leukemia (CML) patients

Authors
Saeid Solali 1
Saeid Kaviani 2
Ali Akbar Movassaghpuor 3
Mohammad Reza Ali-parasti 4
Masoud Soleimani 5
Mehrdad Noruzinia 5
Saeid Abroun 5
Zeinab Kaviani 6
1 Department of Hematology, Faculty of Medical Science, Tarbiat Modares University, Tehran, Iran
2 Assistant Professor, Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran P.O.Code: 1411713116
3 Assistant Professor, Hematology and Oncology Research Center, Tabriz University of Medical Science, Tabriz, Iran
4 Department of Immunology, Faculty of Medical Science, Tabriz University of Medical Science, Tabriz, Iran
5 Assistant Professor, Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
6 M.D. Student, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Abstract
Objective: In this study quantitative expression of MDR1 and hOCT1 genes in CML patients and normal people were measured using Real-Time PCR.
Materials and Methods: To study quantitative expression of these genes by real-time PCR, master-mix with syber green was used. Peripheral blood samples from 30 CML patients and 27 normal persons were harvested. Real-time PCR results were analyzed with relative quantification method.
Result: This study showed that in the patients group who were under treatment with Imatib, MDR1 gene expression was increased which was statistically significant. This increase has a direct relation with disease progress. Gene expression in AP and BP patients was also higher than CP patients. In contrast, hOCT1 expression in patients group in comparison with normal group was not statistically significant.
Conclusion: MDR1 increase in leukemic cell membrane results in the reduction of intra-cellular drug concentration. Thus, optimal concentration of drug for inhibition of BCR-ABL tyrosine kinase is not achieved which culminated in disease progression to AP and BP phases. Moreover changes in hOCT1 gene expression as an influx transporter of Imatib could affect intracellular concentration of drug and finally determine therapy outcome. However, in this study hOCT1 gene expression was variable and was not statistically significant.

Keywords

Pathobiology Reserach
Volume 14, Issue 1
January 2011
Pages 49-57