Patterns of DNMT1 Promoter Methylation in Patients with Acute Lymphoblastic Leukemia

Background: Acute lymphoblastic leukemia (ALL) is a clonal malignant disorder characterized by an uncontrolled proliferation of immature T or B lymphocytes. Extensive studies have shown that the epigenetic changes, especially modified DNA methylation patterns in the regulatory regions through the DN...

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Main Authors: Tirdad Rahmani, Mehdi Azad, Bahram Chahardouli, Hajar Nasiri, Mousa Vatanmakanian, Saeid Kaviani
Format: Article
Language:English
Published: Tehran University of Medical Sciences 2016-12-01
Series:International Journal of Hematology-Oncology and Stem Cell Research
Subjects:
Online Access:https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/view/675
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author Tirdad Rahmani
Mehdi Azad
Bahram Chahardouli
Hajar Nasiri
Mousa Vatanmakanian
Saeid Kaviani
author_facet Tirdad Rahmani
Mehdi Azad
Bahram Chahardouli
Hajar Nasiri
Mousa Vatanmakanian
Saeid Kaviani
author_sort Tirdad Rahmani
collection DOAJ
description Background: Acute lymphoblastic leukemia (ALL) is a clonal malignant disorder characterized by an uncontrolled proliferation of immature T or B lymphocytes. Extensive studies have shown that the epigenetic changes, especially modified DNA methylation patterns in the regulatory regions through the DNA methyltransferase (DNMTs), play an important role in the development of genetic disorders and abnormal growth and maturation capacity of leukemic stem cells (LSCs).The aim of this study was to evaluate the changes in DNMT1 promoter methylation and its expression pattern in patients with ALL. Subjects and Methods: In this experimental study, methylation specific PCR (MSP) was used to assess the methylation status of DNMT1 promoter regions in samples collected from ALL patients (n=45) and healthy control subjects. According to this method, un-methylated cytosine nucleotides are converted to uracil by sodium bisulfite and the proliferation of methylated and un-methylated regions are performed using specific primers for target sequences. Results: None of the patients with B and T-ALL showed methylated promoter regions of the DNMT1 gene, while the methylation pattern of both pre-B ALL patients and the control group showed a relative promoter methylation. Conclusion: Analysis of promoter methylation patterns in various subgroups of ALL has revealed the importance of DNMT1 in the regulation of gene expression. Likewise, extensive data have also highlighted the methylation-based mechanisms exerted by DNAM1 as one of the main participants regulating gene expression in B-ALL and T-ALL patients. Investigation of the overall DNA methylation pattern offers significant improvements in the prediction of disease prognosis and treatment response.
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spelling doaj.art-2669c6f65b36422799bd28f603e92d8e2023-09-02T07:03:15ZengTehran University of Medical SciencesInternational Journal of Hematology-Oncology and Stem Cell Research2008-22072016-12-01113Patterns of DNMT1 Promoter Methylation in Patients with Acute Lymphoblastic LeukemiaTirdad Rahmani0Mehdi Azad1Bahram Chahardouli2Hajar Nasiri3Mousa Vatanmakanian4Saeid Kaviani5Department of Hematology, School of Medical Sciences, Tarbiat Modares University, Tehran, IranDepartment of Medical Laboratory Sciences, Faculty of Allied Medicine, Qazvin University of Medical Sciences, Qazvin, IranHematology-Oncology and StemCell Transplantation Research Center, Tehran Universityof Medical Science, Tehran, IranHematology-Oncology and Stem cell Transplantation Research Center, Tehran university of Medical Science, Tehran, Iran. AND Children’s Medical Center, Tehran University of Medical Sciences, Tehran, IranDepartment of Hematology, Faculty of Allied Medicine, Tehran University of Medical Sciences, Tehran, IranDepartment of Hematology, School of Medical Sciences, Tarbiat Modares University, Tehran, IranBackground: Acute lymphoblastic leukemia (ALL) is a clonal malignant disorder characterized by an uncontrolled proliferation of immature T or B lymphocytes. Extensive studies have shown that the epigenetic changes, especially modified DNA methylation patterns in the regulatory regions through the DNA methyltransferase (DNMTs), play an important role in the development of genetic disorders and abnormal growth and maturation capacity of leukemic stem cells (LSCs).The aim of this study was to evaluate the changes in DNMT1 promoter methylation and its expression pattern in patients with ALL. Subjects and Methods: In this experimental study, methylation specific PCR (MSP) was used to assess the methylation status of DNMT1 promoter regions in samples collected from ALL patients (n=45) and healthy control subjects. According to this method, un-methylated cytosine nucleotides are converted to uracil by sodium bisulfite and the proliferation of methylated and un-methylated regions are performed using specific primers for target sequences. Results: None of the patients with B and T-ALL showed methylated promoter regions of the DNMT1 gene, while the methylation pattern of both pre-B ALL patients and the control group showed a relative promoter methylation. Conclusion: Analysis of promoter methylation patterns in various subgroups of ALL has revealed the importance of DNMT1 in the regulation of gene expression. Likewise, extensive data have also highlighted the methylation-based mechanisms exerted by DNAM1 as one of the main participants regulating gene expression in B-ALL and T-ALL patients. Investigation of the overall DNA methylation pattern offers significant improvements in the prediction of disease prognosis and treatment response.https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/view/675Acute lymphocytic leukemiaEpigeneticMethylationDNA methyltransferase
spellingShingle Tirdad Rahmani
Mehdi Azad
Bahram Chahardouli
Hajar Nasiri
Mousa Vatanmakanian
Saeid Kaviani
Patterns of DNMT1 Promoter Methylation in Patients with Acute Lymphoblastic Leukemia
International Journal of Hematology-Oncology and Stem Cell Research
Acute lymphocytic leukemia
Epigenetic
Methylation
DNA methyltransferase
title Patterns of DNMT1 Promoter Methylation in Patients with Acute Lymphoblastic Leukemia
title_full Patterns of DNMT1 Promoter Methylation in Patients with Acute Lymphoblastic Leukemia
title_fullStr Patterns of DNMT1 Promoter Methylation in Patients with Acute Lymphoblastic Leukemia
title_full_unstemmed Patterns of DNMT1 Promoter Methylation in Patients with Acute Lymphoblastic Leukemia
title_short Patterns of DNMT1 Promoter Methylation in Patients with Acute Lymphoblastic Leukemia
title_sort patterns of dnmt1 promoter methylation in patients with acute lymphoblastic leukemia
topic Acute lymphocytic leukemia
Epigenetic
Methylation
DNA methyltransferase
url https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/view/675
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