Expression Analysis of Fyn and Bat3 Signal Transduction Molecules in Patients with Chronic Lymphocytic Leukemia.

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.