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Sci J Iran Blood Transfus Organ 2014, 11(2): 103-109 |
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Mokhberian N, Mahjoubi F, Pourahmad R. Investigation of G2677T/A polymorphism in MDR1 gene of childhood acute lymphoblastic leukemia. Sci J Iran Blood Transfus Organ 2014; 11 (2) :103-109
URL: http://bloodjournal.ir/article-1-788-en.html
URL: http://bloodjournal.ir/article-1-788-en.html
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| Abstract (HTML) (8171 Views)
Investigation of G2677T/A polymorphism in MDR1
gene of childhood acute lymphoblastic leukemia
Mokhberian N.¹, Mahjoubi F.², Pourahmad R.³
1Shahroud University of Medical Sciences, Shahroud, Iran
2National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran
3Shahrekord University, Shahrekord, Iran
Abstract
Background and Objectives
The important reason of drug resistance is ATP dependent pumps such as MDR1 that extrudes drugs from the cell. MDR1 is highly polymorphic. It seems that polymorphisms influence the gene expression and response to treatment. The aim of this study was to investigate G2677T/A polymorphism of the MDR1 gene and its association with the response of treatment in childhood acute lymphoblastic leukemia.
Materials and Methods
In this descriptive study, G2677T/A polymorphism of MDR1 was investigated in 44 children with acute lymphoblastic leukemia and 40 healthy individuals by the ARMS-PCR technique. The association of this polymorphism with response to treatment was also investigated.
Results
In the patient group, the frequencies of genotypes were 36.4% for TT, 41% for GT, 13.6% for GG,4.5% for AG, 2.25% for AT and 2.25 % for AA whereas in the control group the frequencies were 35%, 37.5% , 10%, 7.5%, 5% , and 5% for TT, GT, GG, AG, AT, and AA, respectively. There was no significant difference in the frequencies of G2677T/A polymorphism between patients and the healthy group. Neither was there any significant difference between the frequency rates of G2677T/A polymorphism of MDR1 in the responder and the non responder.
Conclusions
It seems that there is no correlation between G2677T/A polymorphism of MDR1 gene and response to treatment. So the role of G2677T/A polymorphism in the gene expression of MDR1 in childhood acute lymphoblastic leukemia and response to treatment is still controversial.
Key words: Acute Lymphoblastic Leukemia, Drug Resistance, Lymphoblastic, MDR1 Protein
Received: 12 Oct 2013
Accepted: 24 Dec 2013
Correspondence: Mokhberian N., MSc of Genetics. Instructor of Shahroud University of Medical Sciences.
Postal Code: 3614773955, Shahroud, Iran. Tel: (+98273) 3394800 ; Fax: (+98273) 3394800
E-mail:
n_mokhberian@yahoo.com
Full-Text: (1449 Views)
References:
- National Cancer Institute. SEER Cancer Statistics Review, 1975-2008. Available from: http://seer.cancer.gov/archive/csr/1975_2008/.
- WHO. Incidence of childhood leukemia; 2009. Available from: http://www.euro.who.int/__data/assets/pdf_file/0005/97016/4.1.-Incidence-of-childhood-leukaemia-EDITED_layouted.pdf.
- Mousavi SM, Pourfeizi AA, Dastgiri S. Childhood cancer in Iran. J Pediatr Hematol Oncol 2010; 32(5): 376-82.
- Longley DB, Johnston PG. Molecular mechanisms of drug resistance. J Pathol 2005; 205(2): 275-92.
- Gpttes,am MM, Fojo T, Bates SE. Multidrug resistance in cancer: role of ATP-dependent transporters. Nat Rev Cancer 2002; 2(1): 48-58.
- Gottesman MM. Mechanisms of cancer drug resistance. Annu Rev Med 2002; 53 :615-27.
- Dean M, Hamon Y, Chimini G. The human ATP-binding cassette (ABC) transporter superfamily. J Lipid Res 2001; 42(7): 1007-17.
- van der Deen M, de Vries EG, Timens W, Scheper RJ, Timmer-Bosscha H, Postma DS. ATP-binding cassette (ABC) transporters in normal and pathological lung. Respir Res 2005; 6: 59.
- Kimchi-Sarfaty C, Oh JM, Kim IW, Sauna ZE, Calcagno AM, Ambudkar SV, et al. A "silent" polymorphism in the MDR1 gene changes substrate specificity. Science. 2007; 315(5811): 525-8.
- Fung KL, Gottesman MM. A synonymous polymorphism in a common MDR1 (ABCB1) haplotype shapes protein function. Biochim Biophys Acta 2009; 1794(5): 860-71.
- Xing Q, Gao R, Li H, Feng G, Xu M, Duan S, et al. Polymorphisms of the ABCB1 gene are associated with the therapeutic response to risperidone in Chinese schizophrenia patients. Pharmacogenomics 2006; 7(7): 987-93.
- Gréen H1, Falk IJ, Lotfi K, Paul E, Hermansson M, Rosenquist R, et al. Association of ABCB1
polymorphisms with survival and in vitro cytotoxicty in de novo acute myeloid leukemia with normal karyotype. Pharmacogenomics J 2012; 12(2): 111-8. - Stavrovskaya A. Cellular mechanisms of multidrug resistance of tumor cells. Biochemistry (Mosc) 2000; 65(1): 95-106.
- Löwenberg B, Sonneveld P. Resistance to chemotherapy in acute leukemia. Curr Opin Oncol 1998; 10(1): 31-5.
- Schiffer CA. Acute myeloid leukemia in adults. In: Holland JF, Frei E, Bast RC, Kufe DW, Morton DL, Weichselbaum RR. Cancer Medicine. Philadelphia, PA: Lea & Febiger; 1993. p. 1907-17.
- Urayama KY, Wiencke JK, Buffler PA, Chokkalingam AP, Metayer C, Wiemels JL. MDR1 Gene variants, indoor insecticide exposure, and the risk of childhood acute lymphoblastic leukemia. Cancer Epidemiol Biomarkers Prev 2007; 16(6): 1172-7.
- van der Holt B, Van den Heuvel-Eibrink MM, Van Schaik RH, van der Heiden IP, Wiemer EA, Vossebeld PJ, et al. ABCB1 gene polymorphisms are not associated with treatment outcome in elderly acute myeloid leukemia patients. Clin Pharmacol Ther 2006; 80(5): 427-39.
- Kurzawski M1, Droździk M, Suchy J, Kurzawski G, Białecka M, Górnik W, et al. Polymorphism in the P-glycoprotein drug transporter MDR1 gene in colon cancer patients. Eur J Clin Pharmacol 2005; 61(5-6): 389-94.
- Green H, Falk J, Lotfi K, Paul E, Hermansson H, Rosenquistz R, et al. Association of ABCB1 polymorphisms with survival and in vitro cytotoxicty in de novo acute myeloid leukemia with normal karyotype. Pharmacogenomics J 2010; 12(2): 111-8.
- Wang LH, Song YB, Zheng WL, Jianq L, Ma WL. The association between polymorphism in the MDR1 gene and risk of cancer /a systematic review and pooled analysis of 52 casa control studies. Cancer Cell Int 2013; 13(1): 46.
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Sci J Iran Blood Transfus Organ 2014; 11(2): 103-109 |
|
Original Article
|
Investigation of G2677T/A polymorphism in MDR1
gene of childhood acute lymphoblastic leukemia
Mokhberian N.¹, Mahjoubi F.², Pourahmad R.³
1Shahroud University of Medical Sciences, Shahroud, Iran
2National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran
3Shahrekord University, Shahrekord, Iran
Abstract
Background and Objectives
The important reason of drug resistance is ATP dependent pumps such as MDR1 that extrudes drugs from the cell. MDR1 is highly polymorphic. It seems that polymorphisms influence the gene expression and response to treatment. The aim of this study was to investigate G2677T/A polymorphism of the MDR1 gene and its association with the response of treatment in childhood acute lymphoblastic leukemia.
Materials and Methods
In this descriptive study, G2677T/A polymorphism of MDR1 was investigated in 44 children with acute lymphoblastic leukemia and 40 healthy individuals by the ARMS-PCR technique. The association of this polymorphism with response to treatment was also investigated.
Results
In the patient group, the frequencies of genotypes were 36.4% for TT, 41% for GT, 13.6% for GG,4.5% for AG, 2.25% for AT and 2.25 % for AA whereas in the control group the frequencies were 35%, 37.5% , 10%, 7.5%, 5% , and 5% for TT, GT, GG, AG, AT, and AA, respectively. There was no significant difference in the frequencies of G2677T/A polymorphism between patients and the healthy group. Neither was there any significant difference between the frequency rates of G2677T/A polymorphism of MDR1 in the responder and the non responder.
Conclusions
It seems that there is no correlation between G2677T/A polymorphism of MDR1 gene and response to treatment. So the role of G2677T/A polymorphism in the gene expression of MDR1 in childhood acute lymphoblastic leukemia and response to treatment is still controversial.
Key words: Acute Lymphoblastic Leukemia, Drug Resistance, Lymphoblastic, MDR1 Protein
Received: 12 Oct 2013
Accepted: 24 Dec 2013
Correspondence: Mokhberian N., MSc of Genetics. Instructor of Shahroud University of Medical Sciences.
Postal Code: 3614773955, Shahroud, Iran. Tel: (+98273) 3394800 ; Fax: (+98273) 3394800
E-mail:
n_mokhberian@yahoo.com
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