In order to elucidate if signals from the microenvironment could directly modulate the expression of ZAP-70, we cultured primary CLL cells in suspension or co-cultured with BMSC, CD40L and CpG ODN for 48 hours and observed that the percentage of ZAP-70 positive cells was significantly increased (Figure 4C and 4D) (mean % ZAP-70 positive cells: 61.50±7.33 in co-culture vs. 16.91±4.23 in suspension, P<0.01). This evidence concerns the gene CD40LG and B-cell chronic lymphocytic leukemia.