Persistent CD49d engagement in circulating CLL cells: a role for blood-borne ligands?

CD49d, the \u3b1-chain of the integrin heterodimer \u3b14\u3b21 (CD49d/CD29) is expressed on cell surface of ~40% of chronic lymphocytic leukemia (CLL) cases. It mediates both cell\u2013cell and cell\u2013matrix adhesion through binding to the vascular cell adhesion molecule-1 (VCAM-1) and fibronectin (FN), respectively. These interactions regulate CLL cell recirculation from the blood stream to tissue sites, as well as the transmission to CLL cells of signals of pro-survival and resistance to drug-induced apoptosis.1 Consistent with this functional role in CLL, a recent worldwide meta-analysis carried out on a large patient cohort, definitely demonstrated the independent prognostic relevance of CD49d in this diseas