CD38/CD31 interactions activate genetic pathways leading toproliferation and migration in chronic lymphocytic leukemia cells

Human CD38 is a pleiotropic glycoprotein belonging to a family of genes coding for enzymes/receptors involved in the catabolism of extracellular nucleotides. CD38 receptor activities are regulated through binding to the non-substrate ligand CD31. CD38 expression above a critical threshold represents a negative prognostic marker for CLL patients. Activation of CD38 by means of agonistic monoclonal antibodies or the CD31 ligand induces proliferation and immunoblast differentiation of CLL cells. Here we define the genetic signature that follows long-term in vitro interactions between CD38(+) CLL lymphocytes and CD31(+) cells. The emerging profile confirms that the CD31/CD38 axis activates genetic programs relevant for proliferative responses. It also indicates a contribution of this pathway to the processes mediating migration and homing. These results further support the notion that the CD31/CD38 axis is part of a network of accessory signals that modify the microenvironment, favoring localization of leukemic cells to growth-permissive sites.