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

ITGA4 gene methylation status in chronic lymphocytic leukemia

Hanaa Rm Attia  1 , Mona Hamed Ibrahim  1 , Shereen H Abd El-Aziz  1 , Naglaa M Hassan  2 , Randa A Osman  3 , Heba A Hagag  4 , Marianne E Yassa  5 , Amany H Abdelrahman  6 , Iman I Salama  7 , Mohamed Emam Sobeih  8
Affiliations

ITGA4 gene methylation status in chronic lymphocytic leukemia

Hanaa Rm Attia et al. Future Sci OA. .

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.

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Conflict of interest statement

Financial & competing interests disclosure The authors gratefully acknowledge the financial support of the Science and Technology Development Fund (STDF), Egypt through Targeted Health call grant no. 22918 and Capacity Building Grant no. 4880. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

Figures

Figure 1.
Figure 1.. ITGA4; genomic location.
ITGA4 gene specification and chromosome location according to GeneGlobe specification, [21].
Figure 2.
Figure 2.. ITGA4 gene methylation (%) of the four CpG sites by pyrosequencing of some chronic lymphocytic leukemia patients.
Figure 3.
Figure 3.. Comparison between ITGA4 gene methylation (%) of the four CpG sites by pyrosequencing between chronic lymphocytic leukemia patients (n = 81) and controls (n = 75).
The CpG sites-1,2,3 showed significantly higher mean levels in chronic lymphocytic leukemia patients than healthy controls (p = <0.001, 0.007 and 0.009, respectively). Error bars: 95% CI.
Figure 4.
Figure 4.. Receiver operating characteristics curves for the ITGA4 methylation % of the four CpG sites among patients and healthy controls.
ROC: Receiver operating characteristics.
Figure 5.
Figure 5.. Comparison between ITGA4 gene methylation (%) of the four CpG sites by pyrosequencing between different groups of chronic lymphocytic leukemia patients based on B2M levels (patients with B2M >3.5 µg/ml, n = 62; patients with B2M <3.5 µg/ml, n = 19).
Error bars: 95% CI.
See this image and copyright information in PMC

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