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.
Fatemeh Hajighasemi
Abstract
Background: Leukemia is a malignant proliferative disorder of the hematopoietic cells. The important role of angiogenesis in leukemia has been reported by several studies. Matrix metalloproteinases (MMPs) are a large group of endopeptidases which degredate the extracellular matrix and play an important ...
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Background: Leukemia is a malignant proliferative disorder of the hematopoietic cells. The important role of angiogenesis in leukemia has been reported by several studies. Matrix metalloproteinases (MMPs) are a large group of endopeptidases which degredate the extracellular matrix and play an important role in angiogenesis. Objective: The present study was conducted to evaluate the patterns of MMP-2 activity in three leukemic cell lines. Methods: Human leukemic monocyte (U937) and T cells (Molt-4 and Jurkat) were cultured in complete RPMI-1640 medium. The cells were then seeded at a density of 106 cells/ml and were incubated with different concentrations of phorbol myristate acetate (PMA) (1-25 ng/ml) or phytoheamagglutinin (PHA) (2-10 μg/ml) for 24 hours. The MMP-2 activity in cell-conditioned media was then evaluated by gelatin zymography. Statistical comparisons between groups were made by analysis of variance (ANOVA). Results: PHA/PMA significantly and dose-dependently increased MMP-2 activity in U937 cells after 24 hours of incubation compared with untreated control cells. Moreover, PHA/PMA significantly induced MMP-2 activity in Molt-4 and Jurkat cells after 24 hours of incubation in a dose-dependent manner compared with untreated control cells. Conclusion: We conclude that human leukemic Jurkat, U937 and Molt-4 cells could potentially display MMP-2 activity with different degrees. Thus, these cell lines could provide an appropriate system to study the mechanisms regulating MMPs production in leukemia patients.
