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Volume 14, Issue 2 (3-2024)
Iran J Ped Hematol Oncol 2024, 14(2): 78-93 |
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Imanei-Avaz M, Hashemi A S, Ghasemi N, Hekmati Moghaddam S H, Pourrajab F, Barzegar K et al . Changes in the Expression of DNMTs Before and After Treatment with Methotrexate (MTX)/Mercaptopurine (6-MP) in B-Cell ALL Children. Iran J Ped Hematol Oncol 2024; 14 (2) :78-93
URL: http://ijpho.ssu.ac.ir/article-1-797-en.html
URL: http://ijpho.ssu.ac.ir/article-1-797-en.html
Mahmoud Imanei-Avaz 
, Azam Sadat Hashemi , Nasrin Ghasemi , Seyed Hossein Hekmati Moghaddam , Fatemeh Pourrajab , Kazem Barzegar * , Mahmood Vakili
, Azam Sadat Hashemi , Nasrin Ghasemi , Seyed Hossein Hekmati Moghaddam , Fatemeh Pourrajab , Kazem Barzegar * , Mahmood Vakili
English Language Department, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
Abstract: (88 Views)
Background: DNA methylation is catalyzed by DNA methyltransferases (DNMTs) which are encoded by DNMT1, DNMT3A, and DNMT3B. DNMTs play a major role in the abnormal methylation of tumor suppressors and cancer-related genes. Herein, this study explored the expression profile of DNMTs in pediatric patients with B-cell acute lymphoblastic leukemia (ALL), before and after methotrexate (MTX)/mercaptopurine (6-MP) treatment.
Materials and Methods: This before-after prospective study included 30 matched children in sex and age (20 children with B-cell ALL and 10 healthy children used as a control or calibrator group). The expression profile of DNMTs was assessed at two-time points; at the diagnosis time and after MTX/6-MP treatment in the consolidation-maintenance phase of therapy. Notable, all pediatric patients included in this study continued the therapy without adverse events, except two children who were excluded from the study.
Results: The average age of the patient group was 7.1 ± 1.3 years (in the range of 4-9 years), and the average age of the control group was 8.3 ± 1.7 years (6-10 years). The expression profile of DNMTs in B-cell ALL children was obtained completely different from that in the healthy group. After MTX/6-MP treatment of B-cell ALL children, the expression levels of DNMT1 and 3A were increased (p <0.01 & 0.04, respectively), and the expression level of DNMT3B was decreased (p <0.01), significantly.
Conclusions: In ALL, the expression profile of DNMTs would be changed whereby contribute to abnormal growth and maturation capacity of leukemic stem cells and MTX/6-MP treatment could reverse this profile from a cancerous phenotype to the normal one.DNA Methyltransferases (DNMTs), Methotrexate (MTX), Mercaptopurine (6-MP)
Materials and Methods: This before-after prospective study included 30 matched children in sex and age (20 children with B-cell ALL and 10 healthy children used as a control or calibrator group). The expression profile of DNMTs was assessed at two-time points; at the diagnosis time and after MTX/6-MP treatment in the consolidation-maintenance phase of therapy. Notable, all pediatric patients included in this study continued the therapy without adverse events, except two children who were excluded from the study.
Results: The average age of the patient group was 7.1 ± 1.3 years (in the range of 4-9 years), and the average age of the control group was 8.3 ± 1.7 years (6-10 years). The expression profile of DNMTs in B-cell ALL children was obtained completely different from that in the healthy group. After MTX/6-MP treatment of B-cell ALL children, the expression levels of DNMT1 and 3A were increased (p <0.01 & 0.04, respectively), and the expression level of DNMT3B was decreased (p <0.01), significantly.
Conclusions: In ALL, the expression profile of DNMTs would be changed whereby contribute to abnormal growth and maturation capacity of leukemic stem cells and MTX/6-MP treatment could reverse this profile from a cancerous phenotype to the normal one.DNA Methyltransferases (DNMTs), Methotrexate (MTX), Mercaptopurine (6-MP)
Type of Study: Research |
Subject:
biochemistry
Received: 2023/07/16 | Accepted: 2024/02/18 | Published: 2024/03/20
Received: 2023/07/16 | Accepted: 2024/02/18 | Published: 2024/03/20
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