مقالات پذیرفته شده در هفتمین کنگره بین المللی زیست پزشکی
Evaluation of the Effect of the Cytarabine drug on Expression of HOXA-AS2 in Acute lymphoblastic leukemia
Evaluation of the Effect of the Cytarabine drug on Expression of HOXA-AS2 in Acute lymphoblastic leukemia
Neda Zahmatkesh,1Shahine Mirzaei,2Golnaz Asaadi Tehrani,3,*Sina Mirza Ahmadi4,4
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: Children, adolescents, and young adults comprise 70% of ALL cases. The incidence of ALL in United States (US) is 1.8 per 100,000 for all age groups and 5 per 100,000 for ages 0–19. While the incidence in Europe is comparable to the US, data suggest higher incidence in Mexico and other Latin American countries. Survival in ALL is strongly influenced by age with five-year overall survival being 80% in <50 years and <35% in >50 years. T-ALL comprises 15–25% of ALL cases in children and adults. Therefore, T-ALL is primarily a disease of children and young adults and rare in older adults. Sequential accumulation of genomic lesions in the immature T cell progenitors culminates in leukemic transformation and a high proliferative index translates clinically to leukocytosis and extramedullary disease, including large mediastinal/thymic masses and central nervous system (CNS) involvement. The genomic and molecular aberrations seen in T-ALL are distinct from that of B-ALL, yet, up until recently, similar treatment regimens were used for both diseases. The distinction between T-ALL and T-lymphoblastic lymphoma (T-LBL) depends on the degree of bone marrow involvement, with T-ALL cases defined by 20% or more blasts in the bone marrow, whereas T-LBL cases have less than 20% bone marrow blasts with predominance of extramedullary disease. One of the most successful and often used antineoplastic medications is still cytarabine. Arac 's unique metabolism and inactivation by aldehyde dehydrogenase are responsible for its distinct cytotoxic properties. This study aimed to see how cytarabine affected the expression of the HOXA-AS2 gene in acute lymphoblastic leukemia.
Methods: In this research, Two Arac concentrations were created for the current study: 1 and 5 µM at 24 hours. After purchasing the Jurkat E6.1 cell line from the Pasteur Institute, it was given a prepared dose of Arac 24 hours 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 72h of Arac 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 5µM decrease were statistically significant These changes included 1µM (0/903) and 5µM (0/868) at 24 hours, respectively. (P <0.001)
Conclusion: According to the present study results, alternation in HOXA-AS2 expression after treatment with Arac, at two concentration were effective in the decrease of HOXA-AS2 expression. Evidence showed that Arac has positive potential and efficacy because the drug was effective in decreasing gene expression in both concentrations in 24 hours. Therefore, Arac can be a useful drug in controlling the expression of genes involved in leukaemia.