Çocukluk Çağı Akut Lenfoblastik Lösemisi ile Multi Drug Resistance 1 Geni Ekspresyonu Arasındaki İlişki
Abstract
Abstract Association Between Childhood Acute Lymphoblastic Leukemia and Multi Drug Resistance 1 Gene Expression Aim: Cross-resistance of a tumor cell developed against structurally and functionaly different drugs is called Multi Drug Resistance (MDR). It\'s reported that certain single nucleotide polymorphisms of MDR1 gene altered P-glycoprotein expression when MDR1 gene plays a significant role in this mechanism. Among these single nucleotide polymorphisms, C3435T is one of the most studied polymorphisms. In this study, it was aimed to investigate the association among MDR1 gene C3435T polymorphism, MDR1 mRNA levels, and therapeutic response in the patients receiving chemotherapy following the diagnosis of acute lymphoblastic leukemia. Method: In the study, peripheral blood samples were collected from 53 acute lymphoblastic leukemia patients receiving chemotherapy and subsequently, RNAs were isolated from each sample. Next, isolated RNAs were converted into cDNA by reverse transcriptase polymer chain reaction (RT-PCR). Resultant cDNAs were then amplified using MDR1 gene specific primers by PCR. Expression levels were determined using “Scion Image Beta 4.03” program. In order to determine C3435T polymorphism in MDR1 gene, PCR products were digested with Mbo1 enzyme and genotyped following agarose gel electrophoresis. Results: In our study, a statistically significant difference was found upon comparison of MDR1 gene genotypes with MDR1 gene mRNA levels/beta actine mRNA ratios (p=0.026). Conclusion: As a statistically significant difference exists between MDR1 gene mRNA levels and C3435T polymorphism genotype distribution, it is assumed that C3435T polymorphism might have an important impact on therapeutic response.
References
- Cortes JE, Kantarjian HM. Acute lymphoblastic lcukemia. A comprehensive review with emphasis on biology and therapy. Cum-er 1995;76( l2}:2393v4l7. to Jaınroziak K. Balecrczak E. Smolewski P, Robey RW, Cebula B. Panczyk M, Kowalczyk M. Sxınigielska-Kapion A. Mirowski M, Bates SE, Robak T. Functional C3435T polymorphism ol' MDRl gene: an iınpact on genetic susceptibility anıl clinical outcome ol' childlıood acute lynıplıoblastic leukemia. T Eur J Humana 2004:72(5):314-21.
- Jensen CD. Block G, Bul'fler P. Ma X, Selvin S, Month S. Maternal dietary risk factors in childhood acute lynıphoblastic leukemia (United States). Cancer Causes Comm 2004115((ı):559v70.
- Tamer TB. Sahin G. Arinç E. Association between polymorphisms of EPHXI and XRCC] genes and the risk of childhood acute lymphoblastic leukemia. Arch Taxim 2()12;86(3):43l—9.
- Et'l'erth T. Sauerbrey A, Steinbach D. Gebhart E. Drexler HG, Miyachi H, Clıitambar CR. Becker CM. Zintl F, Htımeny A. Analysis of single nucleotide polymorphism C3435T of the multidrug resistance gene MDR in acute lymphoblastic leukemia. int . Oncel 20032313509— 17. 9.
- Tol—toll G. Corona G. Gigante M. Boiocchi M. Inhibition of
- ng activity and cell cycle-dependent cheınosensitivity to doxorubicin in the nmllidrug—resistant LoVo human colon cancer cell line. EnrJ Cancer 1996;32A(9):i591—7. Pirker R, Wallner ]. Geissler K. Linkesch W. Haas OA. Bettelheiın P. Hopfner M. Scherrer R. Valent P. Havetec L. Ludwig H. Lechner K. MDRI gene expression and treatment outcome in acute myeloitl leukemia. J Natl Cancer hm 1991 ',83i lÜ)î708-l 2. Dong Z. Luo J. Xu W. Clinical significance of multidmg resistance gene (mdrl) expression in patients with acute leukemia. Zlmnglma Zhang Lin Zıt Zhi i997:l9(1):72—5.
Çocukluk Çağı Akut Lenfoblastik Lösemisi ile Multi Drug Resistance 1 Geni Ekspresyonu Arasındaki İlişki
Abstract
Türkçe Özet: Amaç: Belirli bir ajana karşı dirençli olan bir tümör hücresinin yapısal ve fonksiyonel olarak birbirinden farklı ilaçlara karşı geliştirdikleri çapraz dirence çoklu ilaç direnci (Multi Drug Resistance: MDR) adı verilmektedir. MDR1 geni bu olayda önemli rol oynadığında, gendeki bazı tekli nükleotid değişimlerinin P-glikoprotein ekspresyonunu etkilediği bildirilmiştir. Bu tekli nükleotid değişimleri içinde en çok çalışılanlardan birisi C3435T polimorfizmidir. Bu çalışmada da akut lenfoblastik lösemi tanısı alıp kemoterapi gören hastaların MDR1 geni mRNA düzeyleri ile C3435T polimorfizmi ve tedaviye yanıt arasındaki ilişkinin araştırılması amaçlanmıştır. Yöntem: Çalışmada 53 akut lenfoblastik lösemi tanısı konmuş ve kemoterapi alan hastalardan kan alınarak RNA izole edildi. Daha sonra izole edilen RNA\'lar revers transkriptaz polimeraz zincir reaksiyonu ile cDNA\'ya çevrildi. Elde edilen cDNA\'lar MDR1 genine özgü primerler kullanılarak polimeraz zincir reaksiyonuyla çoğaltıldı. Ekspresyon düzeyleri “Scion Image Beta 4.03” programı kullanılarak belirlendi. MDR1 genindeki C3435T polimorfizmini belirlemek için, elde edilen polimeraz zincir reaksiyon ürünleri, Mbo I enzimi ile kesildi ve agaroz jel elektroforezi sonrasında genotiplendirildi. Bulgular: Çalışmamızda, MDR1 geni genotipleri ile MDR1 geni mRNA düzeyi/beta aktin mRNA düzeyi oranları karşılaştırıldığında istatistiksel olarak anlamlı bir farklılık bulundu (p=0.026). Sonuç: MDR1 mRNA düzeyleri ile C3435T polimorfizmi genotip dağılımları arasında istatistiksel olarak anlamlı farklılık bulunduğundan tedaviye yanıtta C3435T polimorfizminin etkisinin önemli olabileceği düşünüldü.
References
- Cortes JE, Kantarjian HM. Acute lymphoblastic lcukemia. A comprehensive review with emphasis on biology and therapy. Cum-er 1995;76( l2}:2393v4l7. to Jaınroziak K. Balecrczak E. Smolewski P, Robey RW, Cebula B. Panczyk M, Kowalczyk M. Sxınigielska-Kapion A. Mirowski M, Bates SE, Robak T. Functional C3435T polymorphism ol' MDRl gene: an iınpact on genetic susceptibility anıl clinical outcome ol' childlıood acute lynıplıoblastic leukemia. T Eur J Humana 2004:72(5):314-21.
- Jensen CD. Block G, Bul'fler P. Ma X, Selvin S, Month S. Maternal dietary risk factors in childhood acute lynıphoblastic leukemia (United States). Cancer Causes Comm 2004115((ı):559v70.
- Tamer TB. Sahin G. Arinç E. Association between polymorphisms of EPHXI and XRCC] genes and the risk of childhood acute lymphoblastic leukemia. Arch Taxim 2()12;86(3):43l—9.
- Et'l'erth T. Sauerbrey A, Steinbach D. Gebhart E. Drexler HG, Miyachi H, Clıitambar CR. Becker CM. Zintl F, Htımeny A. Analysis of single nucleotide polymorphism C3435T of the multidrug resistance gene MDR in acute lymphoblastic leukemia. int . Oncel 20032313509— 17. 9.
- Tol—toll G. Corona G. Gigante M. Boiocchi M. Inhibition of
- ng activity and cell cycle-dependent cheınosensitivity to doxorubicin in the nmllidrug—resistant LoVo human colon cancer cell line. EnrJ Cancer 1996;32A(9):i591—7. Pirker R, Wallner ]. Geissler K. Linkesch W. Haas OA. Bettelheiın P. Hopfner M. Scherrer R. Valent P. Havetec L. Ludwig H. Lechner K. MDRI gene expression and treatment outcome in acute myeloitl leukemia. J Natl Cancer hm 1991 ',83i lÜ)î708-l 2. Dong Z. Luo J. Xu W. Clinical significance of multidmg resistance gene (mdrl) expression in patients with acute leukemia. Zlmnglma Zhang Lin Zıt Zhi i997:l9(1):72—5.
Details
| Primary Language | Turkish |
|---|---|
| Journal Section | Articles |
| Authors | |
| Publication Date | June 1, 2011 |
| Submission Date | June 13, 2014 |
| Published in Issue | Year 2011 Volume: 4 Issue: 2 |
Cite
MEU Journal of Health Sciences Assoc was began to the publishing process in 2008 under the supervision of Assoc. Prof. Gönül Aslan, Editor-in-Chief, and affiliated to Mersin University Institute of Health Sciences. In March 2015, Prof. Dr. Caferi Tayyar Şaşmaz undertook the Editor-in Chief position and since then he has been in charge.
Publishing in three issues per year (April - August - December), it is a multisectoral refereed scientific journal. In addition to research articles, scientific articles such as reviews, case reports and letters to the editor are published in the journal. Our journal, which has been published via e-mail since its inception, has been published both online and in print. Following the Participation Agreement signed with TÜBİTAK-ULAKBİM Dergi Park in April 2015, it has started to accept and evaluate online publications.
Mersin University Journal of Health Sciences have been indexed by Turkey Citation Index since November 16, 2011.
Mersin University Journal of Health Sciences have been indexed by ULAKBIM Medical Database from the first issue of 2016.
Mersin University Journal of Health Sciences have been indexed by DOAJ since October 02, 2019.
Article Publishing Charge Policy: Our journal has adopted an open access policy and there is no fee for article application, evaluation, and publication in our journal. All the articles published in our journal can be accessed from the Archive free of charge.
This work is licensed with Attribution-NonCommercial 4.0 International.