The co-culture of CLL cells herein described therefore induced the upregulation of miR-21 and a subsequent clear downregulation at the mRNA level of PTEN, PDCD4 and PIAS3, pointing towards the direct downmodulation by miR-21 but not ruling out the possibility of other microenvironmental factors involved in the regulation of these tumor suppressors. Here, PDCD4 is linked to B-cell chronic lymphocytic leukemia.