In conclusion, we have shown that stimuli from the microenvironment are capable of regulating the expression of miR-21 and the tumor suppressor genes (PTEN, PDCD4 and PIAS3) in CLL via a signaling pathway involving ZAP-70, MAPK and STAT3 transcription factor which correlates with the induction of survival by the microenvironment. This evidence concerns the gene PDCD4 and B-cell chronic lymphocytic leukemia.