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Published on: December 4, 2018
Expression Analysis of Fyn and Bat3 Signal Transduction Molecules in Patients with Chronic Lymphocytic Leukemia
Fereshteh Hosseini-Valiki1, Saeid Taghiloo2,3, Golvash Tavakolian1
1Gastrointestinal Cancer Research Center, Non-Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran.
Background:
Chronic lymphocytic leukemia (CLL) is correlated with defects in T-cell function resulting imparity in antitumor immune responses. Tim-3 is a co-inhibitory immune checkpoint receptor expressed on exhausted T-cells during tumor progression. Fyn and Bat3 are two important adaptor molecules involved in inhibition and activation of Tim-3 downstream signaling, respectively. In this study, the expression of Tim-3, Fyn, and Bat3 mRNA was evaluated in CLL patients.
Methods:
Peripheral blood mononuclear cells (PBMCs) were isolated from 54 patients with CLL and 34 healthy controls. Total RNA was extracted from all samples and applied for cDNA synthesis. The relative expression of Tim-3, Fyn, and Bat3 mRNA was determined by TaqMan Real-Time PCR using GAPDH as an internal control.
Results:
Tim-3 mRNA expression was not significantly different between CLL patients and healthy controls. Fyn mRNA expression was significantly lower in CLL patients and conversely, Bat3 mRNA expression was higher in CLL patients compared to healthy controls. Interestingly, the mRNA expression of Fyn inhibitory adaptor molecule was remarkably associated with expression of Tim-3 in CLL patients.
Conclusion:
We have highlighted for the first time the expression of Fyn and Bat3 adaptor molecules in CLL patients. Our data demonstrated the strong correlation between the expression of Tim-3 and Fyn inhibitory molecules in CLL implying an important role for Tim-3-Fyn cooperation in induction of T-cell exhaustion.
Insights
In chronic lymphocytic leukemia (CLL), T-cell exhaustion is linked to Tim-3 and Fyn adaptor molecules. This study found lower Fyn and higher Bat3 mRNA in CLL patients, suggesting Tim-3-Fyn cooperation in T-cell exhaustion.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Chronic lymphocytic leukemia (CLL) is associated with impaired T-cell antitumor immunity.
- Tim-3 is an immune checkpoint receptor on exhausted T-cells.
- Fyn and Bat3 are adaptor molecules regulating Tim-3 signaling.
Purpose of the Study:
- To investigate the mRNA expression of Tim-3, Fyn, and Bat3 in CLL patients.
- To explore the role of these molecules in T-cell dysfunction in CLL.
Main Methods:
- Peripheral blood mononuclear cells (PBMCs) were collected from 54 CLL patients and 34 healthy controls.
- RNA was extracted, converted to cDNA, and analyzed for Tim-3, Fyn, and Bat3 mRNA levels using TaqMan Real-Time PCR.
- GAPDH was used as an internal control for gene expression normalization.
Main Results:
- Tim-3 mRNA expression showed no significant difference between CLL patients and controls.
- Fyn mRNA expression was significantly lower in CLL patients.
- Bat3 mRNA expression was significantly higher in CLL patients, with a notable association between Tim-3 and Fyn expression.
Conclusions:
- This study is the first to report Fyn and Bat3 expression in CLL patients.
- A strong correlation between Tim-3 and Fyn expression was observed in CLL.
- These findings suggest a crucial role for Tim-3-Fyn interaction in T-cell exhaustion in CLL.
