Identification of polymorphisms on the MDR1 gene among Turkish population and their effects on multidrug resistance in acute leukemia patients

Date

2005-09-01

Author

Kaya, P
Gündüz, Ufuk
Arpaci, F
Ural, AU
Guran, S

Metadata

Show full item record

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Item Usage Stats

151
views

0
downloads

Multidrug-resistance (MDR) phenotype is a serious limitation to the effective chemotherapeutic treatment of many cancer types, including leukemia. One of the most important proteins, the over-expression of which is responsible for the multidrug-resistance phenotype in many cancer types, is P-glycoprotein. This protein is the product of the MDR1 gene. In previous studies, single-nucleotide polymorphisms (SNPs) C3435T, G2677T, and T-129C in the MDR1 gene were shown to be correlated with lower P-glycoprotein expression in normal tissues. It was suggested that this might have an advantage in cancer chemotherapy by resulting in a low drug-resistance phenotype. The frequencies of these SNPs were studied in 45 acute leukemia patients (25 of which were primary refractory and 20 of which were drug-sensitive) and 17 healthy individuals, forming a Turkish population of 62 individuals. In the first part of the study, these polymorphisms were compared with other populations. Marked differences were apparent between African and Turkish populations for the C3435T polymorphism. On the other hand, similarities were found between other Caucasian/Asian and Turkish populations (P < 0.001). However, for the G2677T polymorphism, the Turkish population is different than Japanese and German populations (P < 0.001). For the T-129C polymorphism, all individuals in the studied population were homozygous for the T/T genotype. In the second part of this study, drug-resistant and drug-sensitive acute leukemia patients were compared for these SNPs. These polymorphisms did not seem to have a significant effect on P-glycoprotein-mediated drug resistance in the patients studied.

Subject Keywords

MDR1, P-glycoprotein, Single-nucleotide polymorphism, SNP, Acute leukemia

URI

https://hdl.handle.net/11511/30403

Journal

AMERICAN JOURNAL OF HEMATOLOGY

DOI

https://doi.org/10.1002/ajh.20427

Collections

Graduate School of Natural and Applied Sciences, Article

Suggestions

OpenMETU
Core

Identification of gene mutations involved in drug resistance in liver cancer using RNA-SEQ data analysis Shojaei, Mona; Atalay, Rengül; Acar, Aybar Can; Department of Bioinformatics (2016) A significant concern in cancer research is the detection of cancer associated somatic mutations. Liver cancer is the 5th most common and 2nd deadliest cancer in the world. Several somatic mutations were previously reported in liver cancer but their relations to chemotherapeutic response was not studied in detail. In this study, the relationship between mutation status and drug treatment response of well-differentiated Huh7 and poorly-differentiated Mahlavu liver cancer cells were analyzed. The RNA-Seq data...
ASSOCIATION OF FLT3 AND NPM1 MUTATIONS IN ACUTE MYELOID LEUKEMIA PATIENTS WITH METABOLOMIC PATTERNS DETERMINED BY MASS SPECTROMETRY Gerekci Yeşilyurt, Selin; Özen, Can; Özçubukçu, Salih; Department of Biochemistry (2022-8-29) Acute Myeloid Leukemia is a hematological cancer with high phenotypic and genotypic heterogeneity. Patients diagnosed with AML are categorized into risk groups based on cytogenetic and molecular abnormality tests, which determine the specific treatment regimes. Since risk status determination takes significant amount of time and some emergency patients require immediate treatment, a method to provide fast clinical data that will be the basis for initial treatment regime is needed in the medical commun...
Expression of Multidrug Resistance 1, Lung Resistance Protein and Breast Cancer Resistance Protein Genes in Chronic Leukemias Iseri, Ozlem D.; Kars, Meltem D.; Mutlu, Pelin; Avcu, Ferit; Ural, Ali U.; Gündüz, Ufuk (2011-01-01) One of the major problems in treatment of leukemias is multidrug resistance, which is already present at diagnosis or develops after chemotherapy. The gene expression levels of multidrug resistance resistance 1 (MDR1), breast cancer resistance protein (BCRP) and lung resistance-resistance protein (LRP) were evaluated in blood samples of 20 CLL and 24 CML patients using RT-PCR. MDR1, BCRP and LRP expression levels were detected in 65%, 20% and 45% of CLL patients, and in 54%, 37% and 25% of CML patients, res...
Effect of MDR modulators verapamil and promethazine on gene expression levels of MDR1 and MRP1 in doxorubicin-resistant MCF-7 cells Donmez, Yaprak; Akhmetova, Laila; Iseri, Ozlem Darcansoy; Kars, Meltem Demirel; Gündüz, Ufuk (2011-04-01) One of the major problems of cancer chemotherapy is the development of multidrug resistance (MDR) phenotype. Among the numerous mechanisms of MDR, a prominent one is the increased expression of membrane transporter proteins, the action of which leads to decreased intracellular drug concentration and cytotoxicity of drugs. Among them, P-gp and MRP1, encoded by MDR1 and MRP1 genes, respectively, have been associated with MDR phenotype. Chemical modulators can be used to reverse MDR. These chemicals can either...
DETERMINATION OF THE RELATIONSHIP BETWEEN DOXORUBICIN RESISTANCE AND WNT SIGNALING PATHWAY IN HELA AND K562 CELL LINES Mutlu, Pelin; Pourianazar, Negar Taghavi; Yucel, Meral; Gündüz, Ufuk (2018-01-01) Activation of the Wnt signaling in some types of cancer and its relation with chemotherapy resistance is a very interesting issue that has been emphasized in recent years. Although, it is known that increase in the activity of beta-catenin is important in blast transformation and drug resistance, the underlying mechanisms are still unclear. In this study, changes in the expression levels of 186 genes that are thought to be important in drug resistance and Wnt signaling pathways were determined by using qPCR...

Citation Formats

P. Kaya, U. Gündüz, F. Arpaci, A. Ural, and S. Guran, “Identification of polymorphisms on the MDR1 gene among Turkish population and their effects on multidrug resistance in acute leukemia patients,” AMERICAN JOURNAL OF HEMATOLOGY, pp. 26–34, 2005, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/30403.