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Immunoglobulin Gene Sequence Analysis In Chronic Lymphocytic Leukemia: From Patient Material To Sequence Interpretation
Published on: November 26, 2018
Upregulation of Galectin-9 and PD-L1 Immune Checkpoints Molecules in Patients with Chronic Lymphocytic Leukemia
Saeid Taghiloo1, Esmaeil Allahmoradi, Reza Ebadi
1Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. Email:asgarianhossein@yahoo.com, raminshf@gmail.com.
Abstract:
Background: Deviation of host immune response by engagement of inhibitory receptors is one of the well-known mechanisms of tumor cells for immune evasion and survival. PD-1/PD-L1 and Tim-3/Gal-9 axes are two major pathways in this area which their contribution has been documented in a variety of malignancies. In this study, Gal-9 and PD-L1 expression was investigated in leukemic cells from patients with Chronic Lymphocytic Leukemia (CLL). Methods: Peripheral blood mononuclear cells (PBMCs) were obtained from 25 untreated CLL patients and 15 sex- and age-matched healthy controls. CLL patients were classified into different clinical stages based on the Rai staging system. Total RNA was extracted from all samples and applied for cDNA synthesis. Relative expression of Gal-9 and PD-L1 mRNA was determined by Real-Time PCR using β-actin as a housekeeping gene. Results: Gal-9 and PD-L1 mRNA was significantly more expressed in CLL patients compared to healthy controls (p<0.0001 and p=0.005, respectively). CLL patients in advanced clinical stages showed higher expression of Gal-9 and PD-L1 in comparison to patients in early clinical stages (p<0.0001 and p=0.004, respectively). Conclusion: Our promising results regarding over-expression of Gal-9 and PD-L1 in CLL patients call future complementary studies to more evaluate and confirm these pathways for immunotherapy approaches of this malignancy. Upregulation of both Gal-9 and PD-L1 in CLL patients with advanced clinical stages introduces them as useful prognostic biomarkers for disease progression.
Insights
Tumor cells evade immune responses via inhibitory receptors like PD-1/PD-L1 and Tim-3/Gal-9. This study found higher Gal-9 and PD-L1 expression in Chronic Lymphocytic Leukemia (CLL) patients, especially in advanced stages, suggesting their role in immune evasion and disease progression.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Tumor cells utilize inhibitory immune receptors to evade host immune responses.
- Key pathways involved in immune evasion include PD-1/PD-L1 and Tim-3/Gal-9.
- These pathways are implicated in the progression of various malignancies.
Purpose of the Study:
- To investigate the expression of Galectin-9 (Gal-9) and Programmed Death-Ligand 1 (PD-L1) in leukemic cells from patients with Chronic Lymphocytic Leukemia (CLL).
- To assess the correlation between Gal-9 and PD-L1 expression levels and clinical stages of CLL.
- To explore the potential of these molecules as therapeutic targets or prognostic biomarkers in CLL.
Main Methods:
- Peripheral blood mononuclear cells (PBMCs) were collected from 25 untreated CLL patients and 15 healthy controls.
- RNA was extracted, and relative mRNA expression of Gal-9 and PD-L1 was quantified using Real-Time PCR.
- Patients were staged according to the Rai staging system.
Main Results:
- Gal-9 and PD-L1 mRNA expression was significantly elevated in CLL patients compared to healthy controls (p<0.0001 and p=0.005).
- CLL patients in advanced clinical stages exhibited higher expression of both Gal-9 and PD-L1 compared to early stages (p<0.0001 and p=0.004).
Conclusions:
- Over-expression of Gal-9 and PD-L1 in CLL suggests their involvement in immune evasion mechanisms.
- These findings warrant further investigation into Gal-9 and PD-L1 as potential targets for CLL immunotherapy.
- Elevated Gal-9 and PD-L1 in advanced CLL stages indicate their utility as prognostic biomarkers for disease progression.
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