• Investigating the Effect of Mercaptopurine on Expression Changes of TUG1 in Acute Lymphoblastic Leukemia
  • Neda zahmatkesh,1 Mahnaz Eskandari,2 Golnaz Asaadi Tehrani,3,* Sina Mirza Ahmadi,4
    1. Msc of Molecular Genetic Department of Genetics, Zanjan Branch, Islamic Azad University, Zanjan, Iran.
    2. Assistant Professor,Biology Research Center, Zanjan Branch, Islamic Azad University, Zanjan, Iran
    3. Assistant professor of Molecular Genetics, Department of Genetics, Zanjan Branch, Islamic Azad University, Zanjan, Iran.
    4. Assistant professor of Molecular Genetics, Department of Genetics, Zanjan Branch, Islamic Azad University, Zanjan, Iran.


  • Introduction: Most commonly affecting children, ALL is a kind of cancer that can also affect adults. Due to unchecked cell proliferation, obstructed differentiation, and obstruction of apoptosis, abnormally cloned leukemia cells accumulate in the bone marrow and other non-hematopoietic tissues, impairing normal hematopoiesis and immune function. Leukemia is a malignant clonal disease of hematopoietic stem and progenitor cells. The discovery of dysregulated molecules linked to leukemia thanks to rapid advancements in cell and molecular biology raises the possibility that the disease is influenced by the heterogeneity of cellular and molecular genetics. LncRNAs have a wide range of biological roles and intricate regulatory mechanisms, are typically found in the cytoplasm or nucleus, and demonstrate great functional variability. By boosting EZH2 recruitment and H3K27me3 levels at the miR-34a promoter in leukemia cells, the TUG1 gene epigenetically inhibits miR-34a expression. 6-mercaptopurine is a key component of the pharmacological therapy used to treat pediatric acute lymphoblastic leukemia (ALL) (6-MP). The therapeutic response to this prodrug is significantly influenced by its intracellular metabolism. The disposal of 6-MP involves a large number of metabolizing enzymes, and active 6-MP metabolites include 6-thioguanine nucleotides (6-TGN) and methylated metabolites, which are mostly methylation by the thiopurine S-methyltransferase enzyme (TPMT). The aim of this study was to investigate the Effect of mercaptopurine on Expression Changes of LncRNA TUG1 in Acute Lymphoblastic Leukemia, the Jurkat E6.1 cell line.
  • Methods: In this research, suitable doses of mercaptopurine were prepared according to the IC50 of the drug which consists of 5 and 10µM. The Jurkat E6.1 cell line was treated with mercaptopurine at 72h after cell passage. The expression changes of LncRNA TUG1 and GAPDH as the housekeeping gene were investigated using Real-Time PCR after RNA extraction and cDNA synthesis. Finally, Rest 2002 Software was used to analyze the data, and Excel was used to create diagrams.
  • Results: The Results of the research showed that after 72h of treatment with mercaptopurine at 5 and 10µM, the expression of TUG1inecreased significantly as compared to the control group. according to the result, doses of 5 and 10µM of mercaptopurine over 72h were the optimal concentrations and time for this drug's effect. The expressions of LncRNA TUG1 were 2.38 and 1.899 at the specified concentrations and times.
  • Conclusion: basis of the results expression changes in TUG1 as a Tumor suppressor gene after treatment with mercaptopurine, both concentrations of the drug successfully increased TUG1 expression. generally, mercaptopurine had a positive effect on the LncRNA TUG1 increased mechanism over 72hour, and this increase in expressions was statistically significant (p-value 0.001). According to evidence, mercaptopurine has a high anticancer potential and affirmative treatment of that. Therefore, the mercaptopurine drug has been effective in the tested concentrations in the Jurkat E6.1 cell line. And it has proven its therapeutic efficiency, although more extensive studies are needed for more definitive results.
  • Keywords: GAPDH, LncRNA TUG1, Jurkat E6.1 cell line, Acute Lymphoblastic Leukemia