Based on our previous work showing a role for Orai1, TRPC1 channels and STIM1 [17, 23] in CE, and to better characterize the autonomous Ca2+ channel influx in CE+ B-CLL cells, three strategies were developed using (1) the Orai1 channel blocker, Synta66 (S66); (2) specific siRNA for Orai1, TRPC1 and STIM1 to modulate CE amplitude; and (3) a quantitative analysis of Orai1, TRPC1 and STIM1 expression by Western-blot. This evidence concerns the gene ORAI1 and B-cell chronic lymphocytic leukemia.