ITGA4 gene methylation status in chronic lymphocytic leukemia

Hanaa Rm Attia; Mona Hamed Ibrahim; Shereen H Abd El-Aziz; Naglaa M Hassan; Randa A Osman; Heba A Hagag; Marianne E Yassa; Amany H Abdelrahman; Iman I Salama; Mohamed Emam Sobeih

doi:10.2144/fsoa-2020-0034

ITGA4 gene methylation status in chronic lymphocytic leukemia

Future Sci OA. 2020 Jun 26;6(7):FSO583. doi: 10.2144/fsoa-2020-0034.

Affiliations

¹ Clinical & Chemical Pathology Department, Medical Division, National Research Centre, Centre of Excellence, Cairo, Egypt.
² Clinical Pathology Department, National Cancer Institute, Cairo University, Cairo, Egypt.
³ Clinical Pathology Department, Flow Cytometry Unit, National Cancer Institute, Cairo University, Cairo, Egypt.
⁴ Cytogenetic Unit - Main Lab., Kasr Al-Ainy School of Medicine, Cairo University, Cairo, Egypt.
⁵ Clinical & Chemical Pathology Department, Kasr Al-Ainy School of Medicine, Cairo University, Cairo, Egypt.
⁶ Clinical & Chemical Pathology Department, National Research Centre, Cairo, Egypt.
⁷ Community Medicine Research Department, National Research Centre, Cairo, Egypt.
⁸ Medical Oncology Department, National Cancer Institute, Cairo University, Cairo, Egypt.

Abstract

Background: We aimed to investigate ITGA4 gene expression pattern and to explore its methylation heterogeneity in chronic lymphocytic leukemia (CLL).

Patients & methods: Eighty one CLL patients and 75 healthy subjects were enrolled and prognostic evaluation of patients was assessed. ITGA4 q-realtime PCR was performed using Applied Biosystems, TaqMan gene expression assay. ITGA4 gene-specific CpG methylation was investigated in real time using pyrosequencing technology.

Results: ITGA4 was differentially expressed in CLL patients. The CpG sites-1, 2 and 3 showed significantly higher mean levels than healthy controls (p = <0.001, 0.007 and 0.009). Significant association between CpG site-1 and CLL has been detected using age-adjusted logistic regression (p < 0.001).

Conclusion: Hypermethylation at ITGA4 gene CpG sites (1,2,3) is a characteristic feature in CLL.

Keywords: ITGA4 gene expression; beta 2 microglobulin; chronic lymphocytic leukemia; cytogenetics; methylation analysis; prognostic markers; pyrosequencing.