Naghinezhad Jalal, Alenabi Anita, Ayatollahi Hossein, Sheikhi Maryam, Sadeghian Mohammad Hadi, Khoshnegah Zahra, Boroumand-Noughabi Samaneh
Department of Hematology and Blood Banking, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Med J Islam Repub Iran. 2023 Jun 17;37:68. doi: 10.47176/mjiri.37.68. eCollection 2023.
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.
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.
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 ( < 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.
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.
急性髓系白血病（AML）是成人中最常见的急性白血病，生存率较低。在本研究中，评估了包括DR4、DR5、FAS、半胱天冬酶8和DNA损伤诱导凋亡抑制因子（DDIAS）在内的5种关键凋亡相关基因在AML患者中的表达水平，并与对照组进行比较，旨在评估它们可能的作用及预后影响。
本横断面研究在马什哈德医科大学癌症分子病理学研究中心进行。共纳入30例新诊断的AML病例和30名健康对照。采用实时聚合酶链反应评估病例组和对照组中DR4、DR5、FAS、DDIAS和半胱天冬酶8基因的表达。从医院记录并通过直接联系患者获取其他必要数据，包括细胞遗传学结果、突变、法美英（FAB）分类和生存情况。使用SPSS软件进行统计分析。在适当情况下，采用曼-惠特尼U检验、皮尔逊相关性检验和t检验。采用Kaplan-Meier法估计总生存期（OS）。
与对照组相比，所有评估基因的表达，包括DDIAS（0.89±0.20）、DR4（0.67±0.24）、DR5（0.72±0.24）、FAS（0.70±0.25）和半胱天冬酶8（0.77±0.20）在AML患者中均显著降低（<0.001）。携带t（16；16）或inv（16）的患者FAS基因表达显著更高，而携带FLT3突变的患者半胱天冬酶8表达较低。评估基因的表达对生存无显著影响。
AML中DR4、DR5、FAS和半胱天冬酶8的表达似乎降低。这些分子的低表达可能有助于AML细胞逃避凋亡，因为它们参与凋亡的启动，使其成为潜在的治疗靶点。
