Volume 34, Issue 238 (10-2024)
J Mazandaran Univ Med Sci 2024, 34(238): 48-56 |
Back to browse issues page
Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
Darvish-Khezri M, Tehrani M, Ghalehnoei H, Taghiloo S, Kahrizi A, Asgarian-Orman H, et al . A Study of Differential Transcriptome Expression in CD8+ T Cells in Chronic Lymphocytic Leukemia. J Mazandaran Univ Med Sci 2024; 34 (238) :48-56
URL: http://jmums.mazums.ac.ir/article-1-21336-en.html
URL: http://jmums.mazums.ac.ir/article-1-21336-en.html
Mahdieh Darvish-Khezri 
, Mohsen Tehrani , Hossein Ghalehnoei , Saeid Taghiloo , Amir Kahrizi , Hossein Asgarian-Orman , Abolghasem Ajami , Reza Valadan
, Mohsen Tehrani , Hossein Ghalehnoei , Saeid Taghiloo , Amir Kahrizi , Hossein Asgarian-Orman , Abolghasem Ajami , Reza Valadan
Abstract: (707 Views)
Background and purpose: Chronic Lymphocytic Leukemia (CLL) is a lymphoproliferative disorder characterized by the clonal and malignant proliferation of mature B-cells within the peripheral blood, bone marrow, and secondary lymphoid tissues. In chronic infections and cancers, T-cells become exhausted due to continuous antigen exposure. This uncontrolled tumor cell growth creates an environment that lacks sufficient oxygen, nutrients, and physical space for normal cells, referred to as the tumor microenvironment. The tumor microenvironment employs multiple mechanisms to suppress the immune system, affecting metabolic pathways in both T-cells and tumor cells. Consequently, inhibitory receptors on T-cells and their ligands on tumor cells are upregulated, leading to reduced proliferation, cytotoxicity, and production of effector cytokines, such as interferon-gamma, by T-cells. T-cell exhaustion presents a therapeutic challenge in treating many malignancies, including CLL. In CLL, T-cell exhaustion is observed through the simultaneous upregulation of inhibitory receptors. Given that current therapies for CLL are often associated with side effects, resistance, and relapse, studying transcript changes may assist in designing more effective treatment strategies. This study investigates the transcriptome profile of CD8+ T-cells in CLL patients compared to healthy individuals using bioinformatics platforms.
Materials and methods: The keywords used in this study were CLL, CD8, and human. Raw data were initially searched in the SRA database using these keywords. Left and right reads were merged using CLC Genomics Workbench version 21. Following quality control of the data, sequences were assembled using human genome reference data, mRNA sequences, and coding sequences (CDS). Gene expression related to CD8+ T-cell exhaustion was then compared between CLL patients and healthy individuals. The analysis results were presented in heatmap and volcano plot formats.
Results: In this study, genes involved in CD8+ T-cell exhaustion and differential expression were identified by comparing 11 CLL patients with 11 healthy individuals. The expression levels of 59 selected genes were displayed in volcano plot and heatmap formats. Expression changes in 42 genes were statistically significant (FDR P<0.05), with 18 genes showing increased expression and 24 showing decreased expression in CLL patients compared to healthy controls.
Conclusion: The study found differences in the expression levels of genes involved in CD8+ T-cell exhaustion between CLL patients and healthy individuals. Molecules encoded by genes upregulated in CLL may serve as potential targets for developing new therapies. By creating monoclonal antibodies and small molecules to inhibit these targets, it may be possible to counteract T-cell exhaustion, representing a promising advance in the treatment of this phenomenon.
Materials and methods: The keywords used in this study were CLL, CD8, and human. Raw data were initially searched in the SRA database using these keywords. Left and right reads were merged using CLC Genomics Workbench version 21. Following quality control of the data, sequences were assembled using human genome reference data, mRNA sequences, and coding sequences (CDS). Gene expression related to CD8+ T-cell exhaustion was then compared between CLL patients and healthy individuals. The analysis results were presented in heatmap and volcano plot formats.
Results: In this study, genes involved in CD8+ T-cell exhaustion and differential expression were identified by comparing 11 CLL patients with 11 healthy individuals. The expression levels of 59 selected genes were displayed in volcano plot and heatmap formats. Expression changes in 42 genes were statistically significant (FDR P<0.05), with 18 genes showing increased expression and 24 showing decreased expression in CLL patients compared to healthy controls.
Conclusion: The study found differences in the expression levels of genes involved in CD8+ T-cell exhaustion between CLL patients and healthy individuals. Molecules encoded by genes upregulated in CLL may serve as potential targets for developing new therapies. By creating monoclonal antibodies and small molecules to inhibit these targets, it may be possible to counteract T-cell exhaustion, representing a promising advance in the treatment of this phenomenon.
Keywords: Chronic Lymphocytic Leukemias, T Cell Exhaustion, CD8-Positive T-Lymphocyte, Transcriptome Analyses, Bioinformatics
Type of Study: Research(Original) |
Subject:
Immunology
Send email to the article author
| Rights and permissions | |
 |
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
Articles Copyright © The Author(s). Owned by Mazandaran University of Medical Sciences.
Contact Us
Address: Journal Office, Building No. 2, Mazandaran University of Medical Sciences, Moallem Square, Sari.Tel: +98 (011)34484874 Postal code: 48175-866 E-Mail: jmums@mazums.ac.ir Telefax: +98 (011)33262679
