DNA Methylation and the Expression of the Tumor-Suppressor Genes Protocadherin-10 and Reprimo in Pediatric Acute Lymphoblastic Leukemia

Zahra  Moradi; Mahmood  Barati; Mehdi  Azad; Alieh  Safari; Bahram  Chahardouli; Mohammad Reza  Rezvany

doi:10.18502/ijpho.v13i2.12342

Zahra Moradi Department of Hematology, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran.
Mahmood Barati Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Medical Biotechnology, Faculty of allied Medicine, ,Iran University of Medical Sciences, Tehran, Iran.
Mehdi Azad Department of Medical laboratory Sciences, Qazvin University of Medical Sciences, Qazvin, Iran.
Alieh Safari Department of Pediatrics, Pediatrics Center of Excellence, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
Bahram Chahardouli Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran, Iran.
Mohammad Reza Rezvany Department of Hematology, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran.

DOI: https://doi.org/10.18502/ijpho.v13i2.12342

Keywords: Acute lymphoblastic leukemia, Methylation, PCDH10, RPRM

Abstract

Background: Acute lymphoblastic leukemia (ALL) is the most prevalent hematologic malignancy among children. DNA methylation is well known to play a role in the initiation and progression of cancer. This research aimed to characterize the epigenetic inactivation and gene expression of Protocadherin-10 (PCDH10) and Reprimo (RPRM) in pediatric acute lymphoblastic leukemia, which is associated with epigenetic silencing in human cancers.

Materials and Methods: This case-control study included 21 children (mean age, 4.5 years) with new cases of ALL. In addition, 15 patients with ALL were selected following treatment. Samples of bone marrow were extracted from each patient. Prior to and following treatment, 15 paired samples were analyzed. In addition, ALL patients were compared to 18 normal controls in a case study. MS-HRM and quantitative real-time PCR were utilized to examine the DNA-promoter methylation and gene expression of two TSGs from each group.

Results: Expression of PCDH10 was significantly up regulated in treatment ALL group compared to the new cases of ALL patients (P= 0.0119), PCDH10 gene expression was higher in the normal control group than in the new cases of ALL (P <0.0001). RPRM gene, also had a slightly increase in gene expression in treatment ALL group compared to the new cases of ALL (P =0.0412). RPRM gene expression was higher in the normal control group than in the new cases of ALL) P = 0.0372). There was an increase in methylation in both PCDH10 and RPRM genes in new cases of ALL groups compared with treatment ALL group and normal group (P<0.0001 for both genes).

Conclusions: New cases of ALL were associated with high DNA methylation level and low gene expression of PCDH10 and RPRM genes.