Expression of DR4, DR5, FAS, Caspase-8 and, DDIAS Genes in AML Patients

Jalal Naghinezhad; Anita Alenabi; Hossein Ayatollahi; Maryam Sheikhi; Mohammad Hadi Sadeghian; Zahra Khoshnegah; Samaneh Boroumand-Noughabi

doi:10.47176/mjiri.37.68

Expression of DR4, DR5, FAS, Caspase-8 and, DDIAS Genes in AML Patients

Med J Islam Repub Iran. 2023 Jun 17:37:68. doi: 10.47176/mjiri.37.68. eCollection 2023.

Authors

Jalal Naghinezhad^{1

2}, Anita Alenabi³, Hossein Ayatollahi^{1

4}, Maryam Sheikhi⁴, Mohammad Hadi Sadeghian^{1

4}, Zahra Khoshnegah¹, Samaneh Boroumand-Noughabi^{1

4}

Affiliations

¹ Department of Hematology and Blood Banking, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
² Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
³ Department of Pathology, Shiraz University of Medical Sciences, Shiraz, Iran.
⁴ Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Abstract

Background: Acute myeloid leukemia (AML) is the most common acute leukemia in adults and accompanies a worse survival. In this study, gene expression levels of 5 key players of apoptosis, including DR4, DR5, FAS, caspase 8, and DNA damage-induced apoptosis suppressor (DDIAS), have been evaluated in AML patients compared with controls, aiming to evaluate their possible role and prognostic impact.

Methods: This cross-sectional study was performed in the Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences. A total of 30 newly diagnosed AML cases as well as 30 healthy controls enrolled in the study. Real-time polymerase chain reaction was used to evaluate the expressions of DR4, DR5, FAS, DDIAS, and caspase 8 genes in cases and controls. Other necessary data, including cytogenetic findings, mutations, French-American-British (FAB) classification, and survival, were retrieved from hospital records and by direct contact with patients. Statistical analysis was done by SPSS software. When appropriate, the Mann-Whitney U, Pearson's correlation, and the t tests were utilized. Overall survival (OS) was estimated using the Kaplan-Meier method.

Results: The expression of all evaluated genes, including DDIAS (0.89 ± 0.20), DR4 (0.67 ± 0.24), DR5 (0.72 ± 0.24), FAS (0.70 ± 0.25), and Caspase 8 (0.77 ± 0.20) were significantly decreased in AML patients compared with the controls (P < 0.001). Patients with the t (16;16) or inv (16) expressed significantly higher amounts of the FAS gene and those with FLT3 mutation exhibited lower expression of caspase 8. Expression of the evaluated genes showed no significant effect on survival.

Conclusion: The expression of DR4, DR5, FAS, and caspase 8 seems to be decreased in AML. Lower expression of these molecules may aid AML cells in avoiding apoptosis because they are involved in the initiation of apoptosis, making them potential targets for treatment.

Keywords: Acute Myeloid Leukemia; Apoptosis; Caspase 8; DDIAS; DR4; DR5; FAS.