Methylation and Expression Status of The CpG-Island of SMG1 Promoter in Acute Myeloid Leukemia: A Follow-Up Study in Patients

Document Type : Original Article

Authors

1 Department of Medicine Biotechnology, Faculty of Allied Medicine, Qazvin University of Medical Science, Qazvin, Iran

2 Department of Medical Laboratory Sciences, Faculty of Allied Medicine, Qazvin University of Medical Sciences, Qazvin, Iran

3 Hematology-Oncology and Stem Cell Transplantation Research Center, Shariati Hospital of Tehran, Tehran, Iran

4 Department of Immunology, Pasteur Institute of Iran, Tehran, Iran

5 Metabolic Diseases Research Center, Research Institute for Prevention of Non-Communicable Diseases, Qazvin University of Medical Sciences, Qazvin, Iran

6 Department of Immunology, Tarbiat Modares University, Tehran, Iran

7 Faculty of Allied Medicine, Qazvin University of Medical Sciences, Qazvin, Iran

Abstract

Objective: Aberrant alterations in DNA methylation are known as one of the hallmarks of oncogenesis and play a vital 
role in the progression of acute myeloid leukemia (AML). SMG1 is a member of the Phosphoinositide 3-kinases family, 
acting as a tumor suppressor gene. The aim of this study was the evaluation of the expression level and methylation 
status of SMG1 in AML. 
Materials and Methods: In this follow-up study on AML patients admitted to Shariati Hospital, Tehran, Iran, the methylation status of SMG1 [performed by methylation-specific polymerase chain reaction (PCR)] and its expression 
level (performed by qRT-PCR) were evaluated in three phases: newly diagnosed, under treatment and complete remission. The correlation of the methylation status of SMG1, its expression level, and clinical/paraclinical data was 
analyzed by SPSS ver.25. 
Results: This study on 18 patients and five control individuals showed that the CpG-islands of the SMG1 promoter 
in newly diagnosed cases is hypomethylated compared to the normal group (P=0.002) The fold change of SMG1 expression levels in new cases is 0.464 ± 0.468, while the fold change of SMG1 expression levels in under-treatment and in-remission patients is 0.973 ± 1.159 and 0.685 ± 0.885, respectively. In under-treatment patients, white blood cell (WBC) count decreases 114176.36 cell/µl with each unit of increase in fold change of SMG1 (P<0.0001), and Hb unit increases 2.062 g/dl with each unit of increase in fold change (P<0.0001) Also, in the remission phase, the Hb unit increases 1.395 g/dl with each unit increase in fold change (P=0.019). 
Conclusion: The robust results of our study suggest that the methylation and expression of have a high impact on the pathogenesis of AML. Also, the methylation and expression of SMG1 can play a prognostic role in AML.

Keywords

References

  1. Azad M, Bakhshi Biniaz R, Goudarzi M, Mobarra N, Alizadeh S, Nasiri H, et al. Short view of leukemia diagnosis and treatment in iran. Int J Hematol Oncol Stem Cell Res. 2015; 9(2): 88-94.
  2. Rowe JM. Will new agents impact survival in AML? Best Pract Res Clin Haematol. 2019; 32(4): 101094.
  3. Goudarzi M, Heidary M, Azad M, Fazeli M, Goudarzi H. Evaluation of antimicrobial susceptibility and integron carriage in Helicobacter pylori isolates from patients. Gastroenterol Hepatol Bed Bench. 2016; 9 Suppl1: S47-S52.
  4. Meng H, Cao Y, Qin J, Song X, Zhang Q, Shi Y, et al. DNA methylation, its mediators and genome integrity. Int J Biol Sci. 2015; 11(5): 604-617.
  5. Azad M, Kaviani S, Soleimani M, Nourouzinia M, Hajfathali A. Common polymorphism’s analysis of thiopurine S-methyltransferase (TPMT) in Iranian population. Cell J. 2009; 11(3): 263-347.
  6. Alipour S, Sakhinia E, Khabbazi A, Samadi N, Babaloo Z, Azad M, et al. Methylation status of interleukin-6 gene promoter in patients with Behçet’s disease. Reumatol Clin (Engl Ed). 2020; 16(3): 229- 234.
  7. Pourkarim H, Azad M, Haghi Ashtiani MT, Keshavarz S, Nadali F. The correlation between SMG1 promoter methylation and its expression in acute lymphoblastic leukemia patient. Arch Med Lab Sci. 2016; 2(4): 111-116.
  8. Ghorban K, Shanaki M, Mobarra N, Azad M, Asadi J, Pakzad R, et al. Apolipoproteins A1, B, and other prognostic biochemical cardiovascular risk factors in patients with beta-thalassemia major. Hematology. 2016; 21(2): 113-120.
  9. Vinyard ME, Su C, Siegenfeld AP, Waterbury AL, Freedy AM, Gosavi PM, et al. CRISPR-suppressor scanning reveals a nonenzymatic role of LSD1 in AML. Nat Chem Biol. 2019; 15(5): 529-539.
  10. Vojta A, Dobrinić P, Tadić V, Bočkor L, Korać P, Julg B, et al. Repurposing the CRISPR-Cas9 system for targeted DNA methylation. Nucleic Acids Res. 2016; 44(12): 5615-5628.
  11. Cai SF, Levine RL. Genetic and epigenetic determinants of AML pathogenesis. Semin Hematol. 2019; 56(2): 84-89.
  12. Gholipour H, Abroun S, Noruzinia M, Ghaffari S, Maali A, Azad M. Methylation status of smg1 gene promoter in multiple myeloma. J Blood Cancer. 2018; 10(4): 114-116.
  13. Gubanova E, Brown B, Ivanov SV, Helleday T, Mills GB, Yarbrough WG, et al. Downregulation of SMG-1 in HPV-positive head and neck squamous cell carcinoma due to promoter hypermethylation correlates with improved survival. Clin Cancer Res. 2012; 18(5): 1257-1267.
  14. Ho U, Luff J, James A, Lee CS, Quek H, Lai HC, et al. SMG1 heterozygosity exacerbates haematopoietic cancer development in Atm null mice by increasing persistent DNA damage and oxidative stress. J Cell Mol Med. 2019; 23(12): 8151-8160.
  15. Mai S, Xiao R, Shi L, Zhou X, Yang T, Zhang M, et al. MicroRNA- 18a promotes cancer progression through SMG1 suppression and mTOR pathway activation in nasopharyngeal carcinoma. Cell Death Dis. 2019; 10(11): 819.
  16. Du Y, Lu F, Li P, Ye J, Ji M, Ma D, et al. SMG1 acts as a novel potential tumor suppressor with epigenetic inactivation in acute myeloid leukemia. Int J Mol Sci. 2014; 15(9): 17065-17076.
Cell Journal (Yakhteh)
Volume 24, Issue 4
April 2022
Pages 163-169

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