To assess the clinical significance of the expression of BTLA, CD160, SPN, TIM3, VISTA, and TIGIT in CLL, we analyzed associations of that expression with prognostic factors including the following: the mutational status of the immunoglobulin heavy-chain variable region (IGHV), MYD88, TP53, and NOTCH1, and the expression of the zeta chain of T-cell receptor-associated protein kinase 70 (ZAP-70), CD38, and lactate dehydrogenase (LDH) activity and β2microglobulin level. This evidence concerns the gene SPN and B-cell chronic lymphocytic leukemia.