Volume 16, Issue 3 (September 2024 2024)                   Iranian Journal of Blood and Cancer 2024, 16(3): 40-47 | Back to browse issues page


XML Print


Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Turkmen S, Karami chermahini N, Maali A, Keramati M R, Ahmadi M H, Azad M et al . Evaluation of the CpG-island DNA Methylation Pattern in Promoter of DNMT1 and CDX2 Genes in Different Phases of Acute Myeloid Leukemia; A Follow-up Study. Iranian Journal of Blood and Cancer 2024; 16 (3) :40-47
URL: http://ijbc.ir/article-1-1605-en.html
1- Department of Hematology and Blood Banking, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
2- Department of Medical Biotechnology, Faculty of Allied Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.
3- Department of Medical Biotechnology, Faculty of Allied Medicine, Qazvin University of Medical Sciences, Qazvin, Iran. & Department of Immunology, Pasteur Institute of Iran, Tehran, Iran.
4- Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
5- Department of Medical Laboratory Sciences, Faculty of Allied Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.
6- Department of Medical Laboratory Sciences, Faculty of Allied Medicine, Qazvin University of Medical Sciences, Qazvin, Iran. , Haematologicca@gmail.com
Abstract:   (136 Views)
Background: Aberrant DNA methylation is a key epigenetic alteration observed in multiple cancers. Acute myeloid leukemia (AML), a prominent form of hematopoietic cancer, is characterized by abnormal proliferation and differentiation of myeloid progenitor cells. This study focuses on examining the methylation status of the CpG islands in the DNMT1 and CDX2 promoter regions and exploring their correlation with prognostic hematological laboratory parameters across three phases of AML: newly diagnosed, undergoing treatment, and in remission.
Material and methods: This follow-up case-control study recruited 11 new cases of confirmed AML admitted to Shariati Hospital in Tehran. All patients received AML treatment according to FDA protocol. The samples (peripheral blood) were collected before medication (new case phase), during medication (under treatment phase), and in the remission phase. Then, genomic DNA was extracted and treated with the bisulfite treatment method. Then, methylation-specific PCR (MSP) was conducted to amplify treated DNAs using two methylated and unmethylated primers related to their promoters' DNMT1 and CDX2 CpG- islands. All statistical analysis was performed using SPSS v.25.
Results: The results of the methylation pattern of DNMT1 gene promoter CpG islands in the present study show that the hemimethylated pattern of the DNMT1 gene promoter is predominant in control (100%), new case phase (90.9%), under treatment phase (72.7%), and remission phase (100%). In the case of the CDX2 gene, the unmethylated pattern is predominant in control (57.14%), new case phase (72.7%), under-treatment phase (90.9%), and remission phase (81.8%). These differences were not statistically significant. No methylated pattern was observed in the control group, and different phases of AML were used for DNMT1 and CDX2. Also, the methylation status of DNMT1 and CDX2 were not correlated with prognostic hematological laboratory parameters.
Conclusion: The methylation patterns of CDX2 and DNMT1 are not different in healthy individuals and AML patients, as well as in different phases of AML. Also, the methylation patterns of CDX2 and DNMT1 cannot help determine the prognosis of AML patients through changes in hematological laboratory parameters.
Full-Text [PDF 492 kb]   (63 Downloads)    
: Original Article | Subject: Genetics
Received: 2024/08/13 | Accepted: 2024/09/17 | Published: 2024/09/30

References
1. Swaminathan M, Wang ES. Novel therapies for AML: a round-up for clinicians. Expert review of clinical pharmacology. 2020;13(12):1389-400. [DOI:10.1080/17512433.2020.1850255]
2. Yeh W, Tirado C. Hypodiploidy in AML. Journal of the Association of Genetic Technologists. 2021;47(3):122-6.
3. 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.
4. Maali A, Maroufi F, Sadeghi F, Atashi A, Kouchaki R, Moghadami M, Azad M. Induced pluripotent stem cell technology: trends in molecular biology, from genetics to epigenetics. Epigenomics. 2021;13(8):631-47. [DOI:10.2217/epi-2020-0409]
5. Maali A, Atashi A, Ghaffari S, Kouchaki R, Abdolmaleki F, Azad M. A Review on Leukemia and iPSC Technology: Application in Novel Treatment and Future. Current stem cell research & therapy. 2018;13(8):665-75. [DOI:10.2174/1574888X13666180731155038]
6. Sahmani M, Vatanmakanian M, Goudarzi M, Mobarra N, Azad M. Microchips and their Significance in Isolation of Circulating Tumor Cells and Monitoring of Cancers. Asian Pac J Cancer Prev. 2016;17(3):879-94. [DOI:10.7314/APJCP.2016.17.3.879]
7. Zebardast S, Sahmani M, Mohammadi S, Foroughi F, Dehghani Fard A, Mohammadi Z, et al. The Gene Expression Profile and DNA Methylation Pattern of CDH1 and DNMT1 Genes in Acute Promyelocytic Leukemia (APL). Reports of biochemistry & molecular biology. 2020;8(4):454-7.
8. Mohammadi Z, Azad M, Foroughi F, Khojastehpour S, Gheibi N, Samiee-Rad F, et al. Evaluation of expression level and methylation profile of CXX1 gene in breast cancer tissue blocks. Journal of cancer research and therapeutics. 2021;17(6):1328-34. [DOI:10.4103/jcrt.JCRT_27_20]
9. Maroufi F, Maali A, Abdollahpour-Alitappeh M, Ahmadi MH, Azad M. CRISPR-mediated modification of DNA methylation pattern in the new era of cancer therapy. Epigenomics. 2020;12(20):1845-59. [DOI:10.2217/epi-2020-0110]
10. Karami N, Ahmadi MH, Mohammadi S, Maali A, Alizadeh A, Pishkhan Dibazar SH, Azad M. Methylation and Expression Status of The CpG-Island of SMG1 Promoter in Acute Myeloid Leukemia: A Follow-Up Study in Patients. Cell journal. 2022;24(4):163-9.
11. Amiri S, Atashi A, Azad M, Elmi A, Abbaszade Dibavar M, Ajami M, et al. Upregulation of Pro-inflammatory Cytokine Genes by Parvovirus B19 in Human Bone Marrow Mesenchymal Stem Cells. Biochem Genet. 2020;58(1):63-73. [DOI:10.1007/s10528-019-09928-y]
12. Hoseini M, Sahmani M, Foroughi F, Khazaei Monfared Y, Azad M. Evaluating the Role of PTEN Promoter Methylation in Patients Predisposed to Hypercoagulable States via Methylation Specific PCR. Reports of biochemistry & molecular biology. 2019;7(2):223-9.
13. Hojjatipour T, Sohani M, Maali A, Rostami S, Azad M. Aberrant DNA Methylation Status and mRNA Expression Level of SMG1 Gene in Chronic Myeloid Leukemia: A Case-Control Study. Cell journal. 2022;24(12):757-63.
14. Rahmani T, Azad M, Chahardouli B, Nasiri H, Vatanmakanian M, Kaviani S. Patterns of DNMT1 Promoter Methylation in Patients with Acute Lymphoblastic Leukemia. International journal of hematology-oncology and stem cell research. 2017;11(3):172-7.
15. Sohani M, Rostami S, Azad M, Hojjatipour T, Chahardouli B, Alizadeh S. Promoter Methylation Status and Expression Levels of RASSF1A Gene in Different Phases of Acute Lymphoblastic Leukemia (ALL). International journal of hematology-oncology and stem cell research. 2021;15(1):7-14. [DOI:10.18502/ijhoscr.v15i1.5245]
16. Monzavi N, Zargar SJ, Gheibi N, Azad M, Rahmani B. Angiopoietin-like protein 8 (betatrophin) may inhibit hepatocellular carcinoma through suppressing of the Wnt signaling pathway. Iran J Basic Med Sci. 2019;22(10):1166-71.
17. Azad M, Kaviani S, Soleymani M, Nourouzinia M, Hajfathali A. Common polymorphism's analysis of thiopurine S-methyltransferase (TPMT) in Iranian population. 2009.
18. Najafi M, Alizadeh SA, Azad M, Naserpour Farivar T, Rajaei F, Hotam Sorouri K, et al. Effect of calprotectin subunit S100A9 on the expression and methylation of OCLN in human melanoma cell line A-375. Turkish journal of biology = Turk biyoloji dergisi. 2017;41(6):849-56. [DOI:10.3906/biy-1704-14]
19. Azad M, Kaviani S, Noruzinia M, Mortazavi Y, Mobarra N, Alizadeh S, et al. Gene Expression Status and Methylation Pattern in Promoter of P15INK4b and P16INK4a in Cord Blood CD34 (+) Stem Cells. Iranian journal of basic medical sciences. 2013;16(7):822-8.
20. Kim HJ, Seo EH, Bae DH, Haam K, Jang HR, Park JL, et al. Methylation of the CDX2 promoter in Helicobacter pylori-infected gastric mucosa increases with age and its rapid demethylation in gastric tumors is associated with upregulated gene expression. Carcinogenesis. 2020;41(10):1341-52. [DOI:10.1093/carcin/bgaa083]
21. Graule J, Uth K, Fischer E, Centeno I, Galván JA, Eichmann M, et al. CDX2 in colorectal cancer is an independent prognostic factor and regulated by promoter methylation and histone deacetylation in tumors of the serrated pathway. Clinical epigenetics. 2018;10(1):120. [DOI:10.1186/s13148-018-0548-2]
22. Kawai H, Tomii K, Toyooka S, Yano M, Murakami M, Tsukuda K, Shimizu N. Promoter methylation downregulates CDX2 expression in colorectal carcinomas. Oncology reports. 2005;13(3):547-51. [DOI:10.3892/or.13.3.547]
23. Wang Y, Li Z, Li W, Liu S, Han B. Methylation of promoter region of CDX2 gene in colorectal cancer. Oncology letters. 2016;12(5):3229-33. [DOI:10.3892/ol.2016.5109]
24. Wang Y, Li Z, Li W, Liu S, Han B. Methylation of CDX2 gene promoter in the prediction of treatment efficacy in colorectal cancer. Oncology letters. 2018;16(1):195-8. [DOI:10.3892/ol.2018.8670]
25. Mizuno S, Chijiwa T, Okamura T, Akashi K, Fukumaki Y, Niho Y, Sasaki H. Expression of DNA methyltransferases DNMT1, 3A, and 3B in normal hematopoiesis and in acute and chronic myelogenous leukemia. Blood. 2001;97(5):1172-9. [DOI:10.1182/blood.V97.5.1172]
26. Aslani S, Mahmoudi M, Garshasbi M, Jamshidi AR, Karami J, Nicknam MH. Evaluation of DNMT1 gene expression profile and methylation of its promoter region in patients with ankylosing spondylitis. Clinical rheumatology. 2016;35(11):2723-31. [DOI:10.1007/s10067-016-3403-x]
27. Thoene S, Rawat VP, Heilmeier B, Hoster E, Metzeler KH, Herold T, et al. The homeobox gene CDX2 is aberrantly expressed and associated with an inferior prognosis in patients with acute lymphoblastic leukemia. Leukemia. 2009;23(4):649-55. [DOI:10.1038/leu.2008.355]
28. Khosravi A, Alizadeh S, Jalili A, Shirzad R, Saki N. The impact of Mir-9 regulation in normal and malignant hematopoiesis. Oncology reviews. 2018;12(1):348. [DOI:10.4081/oncol.2018.348]
29. Darvishi M, Mashati P, Khosravi A. The clinical significance of CDX2 in leukemia: A new perspective for leukemia research. Leukemia research. 2018;72:45-51. [DOI:10.1016/j.leukres.2018.07.021]
30. Makita K, Kitazawa R, Semba S, Fujiishi K, Nakagawa M, Haraguchi R, Kitazawa S. Cdx2 expression and its promoter methylation during metaplasia-dysplasia-carcinoma sequence in Barrett's esophagus. World journal of gastroenterology. 2013;19(4):536-41. [DOI:10.3748/wjg.v19.i4.536]

Add your comments about this article : Your username or Email:
CAPTCHA

Send email to the article author


Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

© 2024 All Rights Reserved | Iranian Journal of Blood and Cancer

Designed & Developed by : Yektaweb