Amir Kahrizi; Armin Akbar; Ahmad Najafi; Hossein Asgarian-Omran; Hossein Karami; Mohammad Naderisorki; Alireza Karimi; Mohsen Tehrani
Abstract
Background: Glucose deprivation in T lymphocytes can trigger compensatory metabolic pathways, potentially contributing to T-cell exhaustion. Additionally, it may induce the unfolded protein response (UPR), ultimately resulting in endoplasmic reticulum (ER) stress.Objectives: To examine the transcriptional ...
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Background: Glucose deprivation in T lymphocytes can trigger compensatory metabolic pathways, potentially contributing to T-cell exhaustion. Additionally, it may induce the unfolded protein response (UPR), ultimately resulting in endoplasmic reticulum (ER) stress.Objectives: To examine the transcriptional profiles of endoplasmic reticulum (ER) stress markers and T-cell exhaustion indicators in CD8+ T lymphocytes isolated from B-ALL patients.Methods: Peripheral blood samples were collected from 22 untreated B-ALL patients and 22 healthy controls. Magnetic Activated Cell Sorting (MACS) was used to isolate CD8+ T lymphocytes. The relative gene expression was then assessed using qRT-PCR with primers specific to XBP1, CHOP, GLUT1, and T-bet.Result: The ER stress response was significantly activated in CD8+ T lymphocytes from B-ALL patients, as evidenced by significant increase in both XBP1 and CHOP transcript levels, relative to normal donors. Although GLUT1 mRNA expression was significantly higher than in control groups, T-bet expression showed no significant difference between the two groups..Conclusion: Collectively, our gene expression data suggest ER stress activation in CD8+ T lymphocytes from B-ALL patients. These findings warrant further investigation into ER stress-related signaling pathways and their potential role in promoting T-cell exhaustion in B-ALL.
Maryam Mohammadi; Hossein Asgarian-Omran; Behnam Najafi; Ahmad Najafi; Reza Valadan; Hossein Karami; Mohammad Naderisoraki; Maryam Alizadeforutan; Ramin Shekarriz; Mohsen Tehrani
Abstract
Background: Thymocyte selection-associated high mobility group box protein (TOX) and members of the nuclear receptor 4A (NR4A) are known as transcription factors involved in T cell exhaustion.Objective: To evaluate the mRNA expression of TOX and NR4A1-3 in CD8+ T cells in acute leukemia.Methods: Blood ...
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Background: Thymocyte selection-associated high mobility group box protein (TOX) and members of the nuclear receptor 4A (NR4A) are known as transcription factors involved in T cell exhaustion.Objective: To evaluate the mRNA expression of TOX and NR4A1-3 in CD8+ T cells in acute leukemia.Methods: Blood samples were obtained from 21 ALL and 6 AML patients as well as 20 control subjects. CD8+ T cells were isolated using MACS. Relative gene expression of TOX and NR4A1-3 was then evaluated using qRT-PCR.Results: Comparison of mRNA expression of TOX in CD8+ T cells showed no significant difference among the study groups (p>0.05), while the expression of NR4A1 was significantly lower in AML patients than in the control group (p=0.0006). Also, the expression of NR4A2 and NR4A3 was significantly lower in both ALL (p=0.0049 and p=0.0005, respectively) and AML (p=0.0019 and p=0.0055, respectively) patients.Conclusion: NR4As expressions were found to be lower in CD8+ T cells from patients with AML and ALL compared to controls, whereas the mRNA expression of TOX showed no significant difference. Although TOX and NR4As are associated with CD8+ T cell exhaustion in solid tumors, they might play different roles in acute leukemia, which requires further investigation.
