Evaluation of the Effect of the Mercaptopurine drug on Expression of HOXA-AS2 in Acute lymphoblastic leukemia
Evaluation of the Effect of the Mercaptopurine drug on Expression of HOXA-AS2 in Acute lymphoblastic leukemia
Neda zahmatkesh,1Shahine Mirzaei,2Golnaz Asaadi Tehrani,3,*Sina Mirza Ahmadi,4
1. Msc of Molecular Genetic Department of Genetics, Zanjan Branch, Islamic Azad University, Zanjan, Iran. 2. Msc of Molecular Genetic Department of Genetics, 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: The most typical kind of teenage cancer is leukaemia. Acute lymphocytic leukemia (ALL), makes up around 78% of all. Mercaptopurine is used alone or with other chemotherapy drugs to treat acute lymphocytic leukaemia (ALL; also called acute lymphoblastic leukaemia and acute lymphatic leukaemia; a type of cancer that begins in the white blood cells). Mercaptopurine is in a class of medications called purine antagonists. It works by stopping the growth of cancer cells. The enzyme thiopurine S-methyltransferase (TPMT) is responsible, in part, for the inactivation of 6-mercaptopurine. TPMT catalyzes the methylation of 6-mercaptopurine into the inactive metabolite 6-methylmercaptopurine this methylation prevents mercaptopurine from further conversion into active, cytotoxic thioguanine nucleotide (TGN) metabolites. Certain genetic variations within the TPMT gene can lead to decreased or absent TPMT enzyme activity, and individuals who are homozygous or heterozygous for these types of genetic variations may have increased levels of TGN metabolites and an increased risk of severe bone marrow suppression (myelosuppression) when receiving mercaptopurine. This study aimed to see how Mercaptopurine affected the expression of the HOXA-AS2 gene in acute lymphoblastic leukaemia.
Methods: In this research Two 6mp concentrations were created for the current study: 5 and 10 µM at 24 hours. After purchasing the Jurkat E6.1 cell line from the Pasteur Institute, it was given a prepared dose of 6mp 24h after cell passage. Following RNA extraction and cDNA synthesis, Real-Time PCR was used to examine the changes in the expression of HOXA-AS2 and GAPDH.
Results: The results of our findings showed that the expression of HOXA-AS2 in comparison with the GAPDH housekeeping gene decreased after 24h of 6mp treatment at both of the concentration drugs. According to the findings, changes in HOXA-AS2 gene expression decreased after 24 hours at a concentration of 1µM and 10µM decrease were statistically significant These changes included 5µM (0/915) and 10µM (0/766) at 24 hours, respectively. (P <0.001)
Conclusion: According to the present study results, alternation in HOXA-AS2 expression after treatment with 6mp, at two concentration were effective in the decrease of HOXA-AS2 expression. Evidence showed that 6mp has positive potential and efficacy because the drug was effective in decreasing gene expression in both concentrations in 24 hours. Therefore, 6mp can be a useful drug in controlling the expression of genes involved in leukaemia.