Impact Of TP53 Gene Promoter Methylation On Chronic Lymphocytic Leukemia Pathogenesis And Progression

Waleed Haji Saeed; Adil Abozaid Eissa; Adnan Anwar Al-Doski

doi:10.2147/JBM.S221707

Impact Of TP53 Gene Promoter Methylation On Chronic Lymphocytic Leukemia Pathogenesis And Progression

J Blood Med. 2019 Nov 25:10:399-404. doi: 10.2147/JBM.S221707. eCollection 2019.

Authors

Waleed Haji Saeed¹, Adil Abozaid Eissa², Adnan Anwar Al-Doski²

Affiliations

¹ Department of Nursing, Akre Technical Institute, Duhok Polytechnic University, Duhok, Iraq.
² Department of Pathology, College of Medicine, University of Duhok, Duhok, Iraq.

Abstract

Background: Chronic lymphocytic leukemia (CLL) is a malignant lymphoid disorder that results from the overgrowth of mature-looking lymphoid cells in the blood and lymphatic tissue. Various clinical presentations have been attributed to the disease as a result of the different underlying genetic and epigenetic alterations. The current study has been initiated to study the role of an epigenetic alteration affecting the promoter of the TP53gene on CLL pathogenesis and progression.

Methods: The current study involved 54 newly diagnosed patients presenting with CLL as well as 30 normal individuals as controls. After obtaining verbal consent, data collection was done and the blood collected from all enrolled individuals for hematological investigations as well as for molecular categorization of TP53 methylation status. Methylation-specific polymerase chain reaction (MS-PCR) technique was used to define the methylation status of the TP53 gene promoter that encompasses DNA extraction, bisulfite conversion, conventional PCR amplification, running on agarose gel and documentation. Finally, statistical analysis was done to assess any correlation of the TP53 epigenetic alteration to the disease etiology and the progression.

Results: In the current study, all controls and 42 of 54 patients show unmethylated TP53 gene promoter; on the other hand, the methylated promoter was detected among 12 patients with a p-value of 0.001. TP53 gene promoter methylation significantly linked to reduced platelet count (p-value of 0.047) and advanced stage at presentation (p-value of 0.076). No significant differences were seen among both methylated and unmethylated TP53 promoters in relation to the age of the affected individuals, total white blood cell counts and hemoglobin level of the affected individuals.

Conclusion: The current study revealed a significant correlation of TP53 gene promoter methylation to chronic lymphocytic leukemia pathogenesis and lower platelet counts.

Keywords: TP53 gene promoter; chronic lymphocytic leukemia; epigenetic alteration.