Narjes Mehrvar1, Hassan Abolghasemi2, Mohammad Reza Rezvany3,4, Mohammad Esmaeil Akbari1, Javad Saberynejad5, Azim Mehrvar5,6, Mohammad Ali Ehsani7, Mahyar Nourian6, Ibrahim Qaddoumi8, Abolfazl Movafagh1,9. 1. Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 2. Pediatric Congenital Hematologic Disorders Research Center, Research Institute for Children's Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 3. Hematology department, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran. 4. Department of Oncology-Pathology, Immune and Gene Therapy Lab, Cancer Center Karolinska (CCK), Karolinska University Hospital Solna and Karolinska Institutet, Stockholm, Sweden. 5. AJA University of Medical Sciences, Tehran, Iran. 6. Mahak Hematology Oncology Research Center (Mahak-HORC), Mahak Hospital, Tehran, Iran. 7. Bahrami Hospital, Tehran University of Medical Sciences, Tehran, Iran. 8. Department of Global Pediatric Medicine, St. Jude Children's Research Hospital, Memphis, TN USA. 9. Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Abstract
BACKGROUND: Abnormal expression of ABCC transporter genes has been associated with treatment failure in pediatric patients with acute lymphoblastic leukemia (ALL). The aim of this study was to evaluate the expression pattern of ABCC1-6 and ABCC10 genes in Iranian pediatric patients with ALL relapse and determine the potential predictive value of determining ALL relapse from ABCC expression. METHODS: Patients with ALL were divided into two separate groups, either the case group with relapsed ALL or the control group in which ALL patients have been in progression-free survival for at least 3 years A total of thirty-nine participants (23 with relapsed ALL; 16 controls) were enrolled over 26 months. To determine the levels of ABCC1-6 and ABCC10 transporter gene expression RT-PCR was used. Cumulative doses of the chemotherapy drugs, VCR, DNR and L-ASP, were calculated for each patient. RESULTS: Our findings showed elevated expression of ABCC2-6 and decreased expression of ABCC1 and ABCC10 to be associated with an increased risk of ALL relapse. The mean-fold expression of ABCC2 was significantly increased in the ALL relapse group. Additionally, the expression pattern of the ABCC transporter genes was associated with high doses of three chemotherapy drugs, VCR, DNR and L-ASP. CONCLUSION: Evaluating the expression pattern of ABCC transporter genes may be a potential biomarker for predicting the occurrence of ALL relapse in Iranian pediatric patients and improve cancer prognosis.
BACKGROUND: Abnormal expression of ABCC transporter genes has been associated with treatment failure in pediatric patients with acute lymphoblastic leukemia (ALL). The aim of this study was to evaluate the expression pattern of ABCC1-6 and ABCC10 genes in Iranian pediatric patients with ALL relapse and determine the potential predictive value of determining ALL relapse from ABCC expression. METHODS: Patients with ALL were divided into two separate groups, either the case group with relapsed ALL or the control group in which ALL patients have been in progression-free survival for at least 3 years A total of thirty-nine participants (23 with relapsed ALL; 16 controls) were enrolled over 26 months. To determine the levels of ABCC1-6 and ABCC10 transporter gene expression RT-PCR was used. Cumulative doses of the chemotherapy drugs, VCR, DNR and L-ASP, were calculated for each patient. RESULTS: Our findings showed elevated expression of ABCC2-6 and decreased expression of ABCC1 and ABCC10 to be associated with an increased risk of ALL relapse. The mean-fold expression of ABCC2 was significantly increased in the ALL relapse group. Additionally, the expression pattern of the ABCC transporter genes was associated with high doses of three chemotherapy drugs, VCR, DNR and L-ASP. CONCLUSION: Evaluating the expression pattern of ABCC transporter genes may be a potential biomarker for predicting the occurrence of ALL relapse in Iranian pediatric patients and improve cancer prognosis.
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