Promoter methylation might shift the balance of Galectin-3 & 12 expression in de novo adult acute myeloid leukemia patients

Magda Assem; Rady E El-Araby; Ahmed A Al-Karmalawy; Reem Nabil; Mohamed A M Kamal; Amany Belal; Heba I Ghamry; Mohammed A S Abourehab; Mohammed M Ghoneim; Mohammad Y Alshahrani; Asmaa A El Leithy

doi:10.3389/fgene.2023.1122864

Promoter methylation might shift the balance of Galectin-3 & 12 expression in de novo adult acute myeloid leukemia patients

Front Genet. 2023 Feb 13:14:1122864. doi: 10.3389/fgene.2023.1122864. eCollection 2023.

Authors

Magda Assem¹, Rady E El-Araby^{2

3}, Ahmed A Al-Karmalawy⁴, Reem Nabil¹, Mohamed A M Kamal⁵, Amany Belal^{6

7}, Heba I Ghamry⁸, Mohammed A S Abourehab^{9

10}, Mohammed M Ghoneim¹¹, Mohammad Y Alshahrani^{12

13}, Asmaa A El Leithy¹⁴

Affiliations

¹ Clinical Pathology Department, National Cancer Institute, Cairo University, Cairo, Egypt.
² Division of Oral Biology, Department of Periodontology, Tufts University School of Medicine, Boston, MA, United States.
³ Central Lab, Theodor Bilharz Research Institute (TBRI), Ministry of Scientific Research, Cairo, Egypt.
⁴ Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ahram Canadian University, Giza, Egypt.
⁵ Clinical Pathology Department, El-Hussein University Hospital, Al-Azhar University, Cairo, Egypt.
⁶ Medicinal Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt.
⁷ Department of Pharmaceutical Chemistry, College of Pharmacy, Taif University, Taif, Saudi Arabia.
⁸ Department of Home Economics, College of Home Economics, King Khalid University, Abha, Saudi Arabia.
⁹ Department of Pharmaceutics and Industrial Pharmacy, College of Pharmacy, Minia University, Minia, Egypt.
¹⁰ Department of Pharmaceutics, Faculty of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia.
¹¹ Department of Pharmacy Practice, College of Pharmacy, AlMaarefa University, Ad Diriyah, Saudi Arabia.
¹² Research Center for Advanced Materials Science (RCAMS), King Khalid University, Abha, Saudi Arabia.
¹³ Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia.
¹⁴ College of Biotechnology, Misr University for Science and Technology (MUST), Giza, Egypt.

Abstract

Acute myeloid leukemia (AML) was reported as the most common type of leukemia among adults. Galectins constitute a family of galactose-binding proteins reported to play a critical role in many malignancies including AML. Galectin-3 and -12 are members of the mammalian galectin family. To understand the contribution of galectin-3 and -12 promoter methylation to their expression, we performed bisulfite methylation-specific (MSP)-PCR and bisulfite genomic sequencing (BGS) of primary leukemic cells in patients with de novo AML before receiving any therapy. Here, we show a significant loss of LGALS12 gene expression in association with promoter methylation. The lowest degree of expression was found in the methylated (M) group while the highest degree was in the unmethylated (U) group and the partially methylated (P) group expression lies in between. This was not the case with galectin-3 in our cohort unless the CpG sites analyzed were outside the frame of the studied fragment. We were also able to identify four CpG sites (CpG number 1, 5, 7& 8) in the promoter region of galectin-12; these sites must be unmethylated so that expression can be induced. As far as the authors know, these findings were not previously concluded in earlier studies.

Keywords: PCR; acute myeloid leukemia; galectin-12; galectin-3; promoter methylation.